Verbal and General IQ Associate with Supragranular Layer Thickness and Cell Properties of the Left Temporal Cortex.

The left temporal lobe is an integral part of the language system and its cortical structure and function associate with general intelligence. However, whether cortical laminar architecture and cellular properties of this brain area relate to verbal intelligence is unknown. Here, we addressed this using histological analysis and cellular recordings of neurosurgically resected temporal cortex in combination with presurgical IQ scores. We find that subjects with higher general and verbal IQ scores have thicker left (but not right) temporal cortex (Brodmann area 21, BA21). The increased thickness is due to the selective increase in layers 2 and 3 thickness, accompanied by lower neuron densities, and larger dendrites and cell body size of pyramidal neurons in these layers. Furthermore, these neurons sustain faster action potential kinetics, which improves information processing. Our results indicate that verbal mental ability associates with selective adaptations of supragranular layers and their cellular micro-architecture and function in left, but not right temporal cortex.

Limited bedding and nesting increases ethanol drinking in female rats.

Prenatal opioid exposure (POE) and postnatal adverse experiences are early life adversities (ELA) that often co-occur and increase problematic alcohol (EtOH) drinking during adolescence. We investigated the relationship between POE, postnatal adversity, and adolescent EtOH drinking in rats. We also sought to determine whether ELAs affect alpha-adrenoceptor density in the brain because the noradrenergic system is involved in problematic alcohol drinking and its treatment. We hypothesized that the combination of POE and postnatal adversity will increase alcohol drinking in rats compared to rats with exposure to either adversity alone or to control. We also predicted that POE and postnatal adversity would increase α1-adrenoceptor density and decrease α2-adrenoceptor density in brain to confer a stress-responsive phenotype. Pregnant rats received morphine (15 mg/kg/day) or saline via subcutaneous minipumps from gestational day 9 until birth. Limited bedding and nesting (LBN) procedures were introduced from postnatal day (PD) 3-11 to mimic early life adversity-scarcity. Offspring rats (PD 31-33) were given opportunities to drink EtOH (20 %, v/v) using intermittent-access, two-bottle choice (with water) procedures. Rats given access to EtOH were assigned into sub-groups that were injected with either yohimbine (1 mg/kg, ip) or vehicle (2 % DMSO, ip) 30 min prior to each EtOH access session to determine the effects of α2-adrenoceptor inhibition on alcohol drinking. We harvested cortices, brainstems, and hypothalami from EtOH-naïve littermates on either PD 30 or PD 70 and conducted radioligand receptor binding assays to quantify α1- and α2-adrenoceptor densities. Contrary to our hypothesis, only LBN alone increased EtOH intake in female adolescent rats compared to female rats with POE. Neither POE nor LBN affected α1- or α2-adrenoceptor densities in the cortex, brainstem, or hypothalamus of early- or late-aged adolescent rats. These results suggest a complex interaction between ELA type and sex on alcohol drinking.

C2-C3 vertebral disc angle: An analysis of patients with and without cervical spondylotic myelopathy.

STUDY DESIGN: Retrospective analysis. OBJECTIVE: To define C2-C3 vertebral disc angle (VDA) in patients with and without cervical spondylotic myelopathy. SUMMARY OF BACKGROUND DATA: C2-C3 VDA is a new radiological index of cervical spine alignment. Recent studies have suggested that high postoperative values are associated with greater mechanical complications in patients with cervical spondylotic myelopathy. However, normative values for patients without myelopathy has yet to be defined. METHODS: Patients with and without cervical myelopathy between 2017 and 2019 were included. Inclusion criteria were patients above 18 years of age with antero-posterior (AP) and lateral (LAT) cervical X-rays. In the non-myelopathic group, patients were excluded if they had neurological symptoms or deficits, presence of cervical axial pain, previous spinal surgery, or diagnosis of either spondylolisthesis or scoliosis. In the myelopathic group, patients were excluded if they had previous spinal surgery. Radiological indices evaluated include: C2-C3 disc angle, C2-C7 Cobb angle, C7 sagittal vertical axis, T1 slope. RESULTS: In total, 99 patients without myelopathy and 22 patients with myelopathy were identified and analyzed. In patients without myelopathy, the mean for C2-C3 VDA was 25.9±7.9. For patients with myelopathy, preoperative values were 24.4±10.0 and 27.1±7.9 postoperatively. No statistically significant differences were found between patients with and without myelopathy. C2-C3 disc angle was not correlated with age (R=-0.173). CONCLUSION: This study did not find statistically significant differences in C2-C3 VDA values between patients with and without cervical myelopathy. This study provides normative data for C2-C3 vertebral disc angle in patients with and without cervical spondylotic myelopathy. Furthermore, C2-C3 vertebral disc angle may be independent from age.

Effect of alternative temozolomide schedules on glioblastoma O(6)-methylguanine-DNA methyltransferase activity and survival.

BACKGROUND: O(6)-methylguanine-DNA methyltransferase (MGMT) expression in glioblastoma correlates with temozolomide resistance. Dose-intense temozolomide schedules deplete MGMT activity in peripheral blood mononuclear cells; however, no published data exist evaluating the effect of temozolomide schedules on intracranial tumour MGMT activity. METHODS: Human glioblastoma cells (GBM43) with an unmethylated MGMT promoter were implanted intracranially in immunodeficient rodents. Three weeks later, animals received temozolomide 200 mg m(-2) for 5 days (schedule A, standard dose) or 100 mg m(-2) for 21 days (schedule B, dose intense). RESULTS: Tumour MGMT activity was depleted by day 6 in both treatment groups compared with baseline. O(6)-methylguanine-DNA methyltransferase activity returned to baseline by day 22 in the schedule A group, but remained suppressed in the schedule B group. By day 29, MGMT activity had returned to baseline in both groups. Mean tumour volume was significantly decreased compared with untreated controls with either schedule (P<0.01), although neither schedule was superior (P=0.60). Median survival was 64, 42, and 28 days for schedule A, schedule B, and no drug, respectively (P<0.001 A or B vs control, P=NS A vs B). CONCLUSIONS: Dose-intense temozolomide prolongs tumour MGMT activity depletion compared with standard dosing, however, survival was not improved in this model.

Clinical relevance and implications of antenatal hydronephrosis.

Detailed antenatal sonography was performed on 18766 pregnant women between 1990 and 1994. Antenatal hydronephrosis, defined as an antero-posterior diameter of the renal pelvis (APPD) greater than 5 mm, was detected in 100 cases (0.59%). Sixty four infants had postnatal hydronephrosis at one and/or six weeks after delivery; 21 of these had urological anomalies. Twelve infants had vesico-ureteric reflux. In all refluxing units the APPD of the renal pelvis was less than 10 mm. Three patients had obstruction at the pelviureteric junction (PUJ); all required surgery. Vesico-ureteric reflux is emerging as the most common urological finding in infants with antenatal hydronephrosis and is likely to be missed if kidneys with APPD of less than 10 mm are not further investigated. In contrast, pelvi-ureteric junction obstruction may be overdiagnosed, based only on drainage patterns of dynamic renogram studies.

Characteristics of a benign subtype of dense deposit disease: comparison with the progressive form of this disease.

Pathologic, clinical and serum complement studies were performed on 18 patients with dense deposit disease (DDD). The patients were divided into 3 groups: group A (10 patients who developed end-stage renal failure within 2.9 +/- 1.0 years of onset) group B (3 patients who developed elevated serum creatinines within 6.8 +/- 4.8 years of onset) and group C (5 patients with no evidence of renal insufficiency after 11.0 +/- 1.4 years of follow-up). Renal biopsies from all patients showed intramembranous, electron-dense deposits in glomerular capillary basement membranes. Most group A and B patients presented with a nephritic and/or nephrotic syndrome and followed an active clinical course. In contrast, group C patients presented with either a nephrotic syndrome or asymptomatic proteinuria +/- hematuria and followed a benign course. Sera from group A and B patients contained reduced concentrations of C3 and factor B and large amounts of C3 nephritic factor (NeF) activity. In contrast, serum of group C patients contained normal amounts of C3 and factor B and low levels of C3 NeF activity. These studies show that some patients with DDD (group C) have a benign illness and that they can be identified by serum levels of C3, factor B and C3 NeF activity.

Wilms' tumor and glomerular disease. Occurrence with features of membranoproliferative glomerulonephritis and secondary focal, segmental glomerulosclerosis.

A case of bilateral Wilms' tumor occurred in which a renal biopsy performed for proteinuria showed features of membranoproliferative glomerulonephritis (MPGN) type 1 and focal segmental glomerulosclerosis (FSGS). A review of the literature for similar cases revealed 24 patients with Wilms' tumor associated with glomerular disease; MPGN was present in one of these cases and FSGS in six. In our patient, circulating immune complexes were detected in the serum and likely played a role in the pathogenesis of the MPGN; the FSGS may have resulted from hyperperfusion of the remaining glomeruli in a kidney that was largely replaced by Wilms' tumor.

Persistent gastroesophageal reflux disease after antireflux surgery in children: I. immediate postoperative evaluation using extended esophageal pH monitoring.

PURPOSE: There is a paucity of quantitative and reproducible follow-up data on childhood operations for gastroesophageal reflux disease (GERD). With the development of minimally invasive techniques for antireflux operations in children, there is a need to quantitatively determine immediate outcomes for such operations performed by laparotomy for comparison. METHODS: A retrospective review of 385 children (age range, 1 week to 15 years) who had a primary antireflux operation in a Children's or University Hospital performed by laparotomy between 1983 and 1997, and who also had an extended esophageal pH study performed within the first 12 postoperative weeks, was conducted. The operations performed included Nissen fundoplication (n = 135), Thal fundoplication (n = 195), and Boerema gastropexy (n = 55). An immediate postoperative failure of the operation to control GERD was defined as an abnormal esophageal pH score persisting up to the twelfth postoperative week. RESULTS: Eleven patients (2.9%) were classified as having an immediate postoperative failure of their operation to control GERD. An additional three patients had an abnormal esophageal pH score 2 weeks postoperatively, which subsequently reverted to a normal esophageal pH score by 12 weeks. The immediate postoperative failure rate was 1.5% (2 of 135) for the Nissen fundoplication, 1.5% (3 of 195) for the Thal fundoplication, and 10.9% (6 of 55) for the Boerema gastropexy. A higher failure rate (five patients, 36%) was seen for the first 14 patients who underwent a Boerema gastropexy during the learning curve period for this operation before 1985, and by excluding these patients the failure rate was 2.4% (1 of 41) after 1985. There was no significantly increased probability of immediate postoperative failure in patients with central nervous system disorders, prematurity, repaired esophageal atresia, or gastric emptying abnormalities. Only 5 (36%) of the 14 children with persisting symptoms suggestive of GERD had immediate postoperative failure of their operation. CONCLUSIONS: Extended esophageal pH monitoring during the first 12 postoperative weeks is a helpful tool to assess the immediate outcome of antireflux operations in children because clinical symptoms alone may be unreliable. The immediate failure rate for an antireflux operation performed in children by laparotomy is very low and seems to be unaffected by comorbid factors.

Use of an antineoepitope antibody for identification of type-II collagen degradation in equine articular cartilage.

OBJECTIVE: To develop an antibody that specifically recognizes collagenase-cleaved type-II collagen in equine articular cartilage. SAMPLE POPULATION: Cartilage specimens from horses euthanatized for problems unrelated to the musculoskeletal system. PROCEDURE: A peptide was synthesized representing the carboxy- (C-) terminus (neoepitope) of the equine type-II collagen fragment created by mammalian collagenases. This peptide was used to produce a polyclonal antibody, characterized by western analysis for reactivity to native and collagenase-cleaved equine collagens. The antibody was evaluated as an antineoepitope antibody by ELISA, using peptides +/- an amino acid at the C-terminus of the immunizing peptide. Collagen cleavage was assayed from equine articular cartilage cultured with interleukin-1 (IL-1), +/- a synthetic MMP inhibitor, BAY 12-9566. Cartilage specimens from osteoarthritic and nonarthritic joints were compared for antibody staining. RESULTS: An antibody, 234CEQ, recognized only collagenase-generated 3/4-length fragments of equine type-II collagen. This was a true antineoepitope antibody, as altering the C-terminus of the immunizing peptide significantly decreased competition for binding in an inhibition ELISA. The IL-1-induced release of type-II collagen fragments from articular cartilage was prevented with the MMP inhibitor. Cartilage from an osteoarthritic joint of a horse had increased staining with the 234CEQ antibody, compared with normal articular cartilage. CONCLUSIONS AND CLINICAL RELEVANCE: We generated an antineoepitope antibody recognizing collagenase-cleaved type-II collagen of horses. This antibody detects increases in type-II collagen cleavage in diseased equine articular cartilage. The 234CEQ antibody has the potential to aid in the early diagnosis of arthritis and to monitor treatment responses.

Dealing with depression & anger: reactions of family caregivers.

Family caregivers are the second victims of Alzheimer's disease, often bearing physical, financial, and emotional burdens of which their loved one cannot conceive. These burdens naturally lead to anger, guilt, loneliness, and depression for caregivers. Professional caregivers are in a position to support the families and ease their anxieties.

Feedback on doctors' performance from parents and carers of children: a national pilot study.

OBJECTIVES: To evaluate the reliability and validity of a children's carers' feedback tool, to explore the feasibility of delivering this nationally and to determine acceptability to doctors of this assessment. PARTICIPANTS: 122 UK paediatricians on the specialist register undertaking outpatient consultations. DESIGN: Participants were each sent 50 forms for distribution to carers. Mean scores for each question, and for the overall pilot cohort were returned to participants with verbatim free text comments. Participating paediatricians' views were sought before and after receiving feedback. RESULTS: 122 doctors returned 4415 forms (mean 36 per doctor). All doctors scored highly with scores across all returned forms having a median of 4.58 (IQ range 0.17) where the maximum score was 5. Differences were observed between scores from female compared to male carers (p<0.05), from consultations rated by carer and child compared to carer alone (p<0.05) and from carers who had previously met the doctor compared to those in their first consultation (p<0.001). 'White' doctors received higher ratings than 'non-white' doctors (p<0.05) and white patients rated both white doctors and non-white doctors more highly than non-white patients (p<0.01). A minimum of 25 consultations rated by children's carers are needed for acceptable reliability. 93.9% of participants would be happy to be assessed in this way for the purposes of revalidation. CONCLUSIONS: National delivery of a valid and reliable method of carer feedback is feasible. The scores received and acceptability in these self-selected doctors was high. Confounding variables may influence feedback, so guidance on interpretation may be needed.

The Royal College of Paediatrics and Child Health programme for subspecialty training.

The National Grid is a training scheme that represents a unique partnership between Deaneries and the Royal College of Paediatrics and Child Health (RCPCH) in offering through national competition, equitable access to high quality subspecialty training. Paediatrics is unusual in that within the umbrella Certificate of Completion of Specialist Training in paediatrics there is the potential to train in one of 13 recognised paediatric subspecialties.

Neurologic-developmental sequelae of chronic renal failure in infancy.

Twelve children who have had chronic renal failure since infancy and underwent early dialysis (mean age 18 months) and early transplantation (mean age 28 months) were studied. Although head circumference in all was within the normal range at birth, by 1 year it was greater than 2 SD below the mean in nine, including six in whom it was greater than 3 SD below the mean. Developmentally, eight children were functioning in the subnormal range; four of these were moderately and one severely mentally retarded. It was not possible to determine whether the unfavorable neurologic-developmental outcome was the result of the toxic effects of uremia, malnutrition, or the associated psychosocial and experiential deprivation related to chronic, severe illness. Even minor insults at this vulnerable stage of brain development may produce permanent damage, and institution of therapy as early as possible may be crucial in obtaining a more favorable outcome.

Complications of diazoxide in the treatment of nesidioblastosis.

Two children with hypoglycaemia secondary to hyperinsulinaemia were treated with diazoxide. They suffered serious side effects of cardiac failure and truncal ataxia.