Surgical revascularisation for childhood moyamoya.

PURPOSE: Children with moyamoya disease/syndrome (MM) have a high rate of recurrent arterial ischaemic stroke (AIS) and associated neurological morbidity; surgical revascularisation (SR) has the potential to prevent this. Here we describe our experience of SR for childhood mm. METHODS: This study is a retrospective review of case notes and radiology of children with moyamoya who underwent SR at our centre. RESULTS: Seventy-three children with MM and who had SR were identified, with median age at presentation of 4.75 years (range 0.6-14.5). Children with >1 AIS or transient ischaemic attack (TIA) and who had not infarcted the whole territory of the diseased carotid artery were offered SR, with the primary aim of preventing further AIS. One hundred and thirty-four SR procedures were undertaken: 82 indirect (62.4 %) and 49 (37.6 %) direct procedures with 3 second SR procedures following initial SR. Median age at surgery was 7.3 (1-18.2) years. There was no perioperative mortality. One anticoagulated child developed an intracranial haemorrhage on the fifth post-operative day. Median duration of follow-up was 34 (5-166) months. Three children (4.1 %) had recurrent AIS (one silent) after SR; two with sickle cell disease had intracranial haemorrhage 1.5 and 11 months post-SR. TIAs improved in 42 out of 53 (79.2 %). CONCLUSION: Our experience of SR for paediatric MM is comparable to other large series. SR is safe, and the rate of recurrent AIS after SR is lower than would be anticipated, on the basis of known natural history of MM. There was no observed difference in outcome of recurrent AIS for direct versus indirect procedures in this series.

Cerebral venous sinus thrombosis in children: risk factors, presentation, diagnosis and outcome.

Neuroimaging and management advances require review of indications for excluding cerebral venous sinus (sinovenous) thrombosis (CSVT) in children. Our goals were to examine (i) clinical presentations of CSVT, (ii) prothrombotic risk factors and other predisposing events, (iii) clinical and radiological features of brain lesions in CSVT compared with arterial stroke, and (iv) predictors of outcome. We studied 42 children with CSVT from five European paediatric neurology stroke registries. Patients aged from 3 weeks to 13 (median 5.75) years (27 boys; 64%) presented with lethargy, anorexia, headache, vomiting, seizures, focal signs or coma and with CSVT on neuroimaging. Seventeen had prior chronic conditions; of the 25 previously well patients, 23 had recent infections, eight became dehydrated and six had both. Two children had a history compatible with prior CSVT. Anaemia and/or microcytosis (21 probable iron deficiency, five haemolytic, including two with sickle cell disease and one with beta-thalassaemia) was as common (62%) as prothrombotic disorder (13/21 screened). High factor VIII and homozygosity for the thermolabile methylene tetrahydrofolate reductase polymorphism were the commonest prothrombotic disorders. The superficial venous system was involved in 32 patients, the deep in six, and both in four. Data on the 13 children with bland infarction and the 12 with haemorrhage in the context of CSVT were compared with those from 88 children with ischaemic (AIS) and 24 with haemorrhagic (AHS) arterial stroke. In multiple logistic regression, iron deficiency, parietal infarction and lack of caudate involvement independently predicted CSVT rather than arterial disease. Five patients died, three acutely, one after recurrence and one after 6 months being quadriparetic and blind. Follow-up ranged from 0.5 to 10 (median 1) years. Twenty-six patients (62%) had sequelae: pseudotumour cerebri in 12 and cognitive and/or behavioural disabilities in 14, associated with epilepsy in three, hemiparesis in two and visual problems in two. Eighteen patients, including six with haemorrhage, were anticoagulated. Older age [odds ratio (OR) 1.54, 95% confidence limits (CI) 1.12, 2.13, P = 0.008], lack of parenchymal abnormality (OR 0.17, 95% CI 0.02, 1.56, P = 0.1), anticoagulation (OR 24.2, 95% CI 1.96, 299) and lateral and/or sigmoid sinus involvement (OR 16.2, 95% CI 1.62, 161, P = 0.02) were independent predictors of good cognitive outcome, although the last predicted pseudotumour cerebri. Death was associated with coma at presentation. Of 19 patients with follow-up magnetic resonance (MR) venography, three had persistent occlusion, associated with anaemia and longer prodrome. A low threshold for CT or MR venography in children with acute neurological symptoms is essential. Nutritional deficiencies may be modifiable risk factors. A paediatric anticoagulation trial may be required, after the natural history has been further established from registries of cases with and without treatment.

Effect of growth on the estrogen receptor levels in MCF-7 cells.

MCF-7 cells have been shown to contain estrogen receptor in several cell fractions following homogenization: nuclei, microsomes, and cytosol. The amount of 17 beta-estradiol-binding capacity found in each cellular compartment depended on the inclusion of detergent in homogenization buffers and on the use of 0.25 M sucrose in the nuclear washes. 17 beta-Estradiol receptor (E2R) associated with nuclei (whole nuclei exchange assay, 0.6 M KCl soluble, and that found on membranes sheared from crude nuclear pellets by centrifugation in 0.25 M sucrose buffer) displayed a dissociation constant (Kd) of 0.77 +/- 0.01 (S.D.) nM (n = 7). KdS of the cytoplasmic (microsomes and soluble) receptors were determined to be 0.33 +/- 0.10 nM (n = 9). Exchangeable ligand on partially purified nuclei assumed its highest level in MCF-7 cells during logarithmic growth in serum-containing media (0.8 pmol/micrograms DNA) but declined after the culture reached confluence (0.2 pmol/micrograms DNA). Seventy-five % of the nuclear E2R declined linearly after feeding MCF-7 cells in logarithmic growth phase an estrogen- and serum-free medium (t1/2 3.5 days). Another class of salt-extractable nuclear receptor (0.2 pmol/micrograms DNA) persisted in postconfluent cultures whether fed estrogen (serum-containing media) or not (serum-free media). This residual binding capacity remained in nuclei of MCF-7 cells for an extended period of time. MCF-7 cells demonstrated functionality of E2R throughout their growth phases as evidenced by the replenishment of cytosolic E2R and the induction of progesterone receptor when given 17 beta-estradiol.

Combined effects of 1,25-dihydroxyvitamin D3 and platinum drugs on the growth of MCF-7 cells.

The effects of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and platinum treatments (both singly and combined) on the growth inhibition of MCF-7 cells, an epithelial cell line shown to possess specific receptors for 1,25(OH)2D3, were evaluated. The inhibitory effects of 1,25(OH)2D3 and platinum on MCF-7 cell proliferation in vitro were time and dose related. The data showed that 10 nM and 100 nM 1,25(OH)2D3 inhibited MCF-7 cell growth by 10.8 +/- 2.4% and 34.9 +/- 0.5% (mean +/- SE), respectively. The degrees of growth inhibition induced by 0.2 to 200 micrograms/ml of cis-diammine-1,1-cyclobutane dicarboxylatoplatinum(II) (carboplatin) were slightly less than those induced by 0.02 to 20 micrograms/ml of cis-diamminedichloroplatinum(II) (cisplatin). The combined administration of 10 nM and 100 nM 1,25(OH)2D3 with either carboplatin (200 to 0.2 micrograms/ml) or cisplatin (20 to 0.02 micrograms/ml) was evaluated. Addition of 1,25(OH)2D3 to the platinum resulted in marginal to marked enhancement of growth inhibition over that observed with either platinum alone. The strength of these interactions varied inversely with the dose of the platinum drugs. Evaluation of drug interactions with isobolograms showed that at near-serum levels, carboplatin or cisplatin interacted synergistically with 1,25(OH)2D3 to inhibit MCF-7 cell growth. Our findings suggest potential usefulness in combining 1,25(OH)2D3, a biological modifier, with cytotoxic agents for the treatment of malignant disease.

Endocarditis related to transvenous pacemakers. Syndromes and surgical implications.

Two cases of microbial endocarditis related to transvenous pacemakers illustrate syndromes whose pathogenesis we consider to be distinctive. Acute Pseudomonas aeruginosa endocarditis related to a pacemaker developed in a 75-year-old man, an event which to our knowledge has not been previously described. There was no evidence of generator site infection, and the sequence of events indicated metastatic implantation of bacteria on traumatized endothelium. A 76-year-old women with a 3 year history of local generator site infection and recurrent fever was found to have extensive vegatative Staphylococcus epidermidis endocarditis at cardiotomy. The sequence of events indicated gradual spread of infection locally, related to the contaminated foreign body. Awareness of these separate pathogenetic mechanisms should facilitate recognition and appropriate management. Removal of the entire pacing system and prolonged antibiotic therapy were considered to be essential to cure of infection in both instances.

Are race differences in the prevalence of hypertension explained by body mass and fat distribution? A survey in a biracial population.

Body mass and body fat distribution are important considerations in the study of hypertension. However, few studies have investigated the relationships with regards to race differences in elevated arterial pressure. A population-based sample of black and white adults was assessed by interview and physical measurement. The prevalence of hypertension (defined as 140/90 mmHg and/or medically treated) was disproportionately higher among blacks than whites. In addition, blacks had a higher prevalence of the more severe hypertension (160/95 mmHg) and hypertension with higher prevalence at earlier ages than whites. Black females had a significantly higher distribution of body mass index (BMI) than white females, while no difference was found in the distributions of males. White males had a higher distribution of waist to hip ratio (WHR) than black males, while black females had the higher values compared to white females. The prevalence of hypertension increased with BMI and WHR. Blacks maintained higher rates of hypertension after controlling for BMI and WHR, however, the margin of difference diminished when BMI and WHR was considered together. The black-white difference in hypertension was not completely explained by BMI and WHR. In addition, the strength of the association of hypertension and body size was different for blacks and whites which suggests possible differences in the mechanisms regulating blood pressure.

Reversal of alcohol's effects on neurite extension and on neuronal GAP43/B50, N-myc, and c-myc protein levels by retinoic acid.

Alcohol teratogenesis may be due in part to inhibition of neuronal differentiation by ethanol. We showed previously that alcohol decreased neuronal differentiation (neurite extension) and increased N-myc and c-myc neuronal protein levels. Since Growth-Associated Protein 43 (GAP43/B50) levels must increase for neurons to differentiate, alcohol may decrease GAP43/B50. Alcohol dose-dependently (0-0.5%) decreased GAP43/B50 protein levels by up to 92% in immature LA-N-5 cells. Five nM retinoic acid alone induced differentiation and increased GAP43/B50 levels to 230% of control. These retinoic acid-induced increases in GAP43/B50 and neurite outgrowth, and decreases in N-myc and c-myc, were reversed dose-dependently by alcohol (0-0.5%). Conversely, the adverse effects of 0.25% alcohol on neurite extension, GAP43/B50, N-myc, and c-myc were prevented by 15 and 45 nM retinoic acid. These results suggest that inhibition of neuronal differentiation by alcohol and prevention of such effects by retinoic acid are related to changes in GAP43/B50, N-myc and c-myc.

Exposure of embryonic cells to alcohol: contrasting effects during preimplantation and postimplantation development.

Alcohol is a known teratogen that causes a broad variety of developmental anomalies, including fetal growth retardation, craniofacial anomalies, and neurological disorders. The etiology of this multiple defect syndrome, known as fetal alcohol syndrome, has been studied in animal models that reproduce many of the attributes of the human disease. These studies show that ethanol is most teratogenic during organogenesis and development of the nervous system. The molecular basis of fetal alcohol effects has been further investigated using embryo and cell culture systems. Recent studies show that signal transduction pathways controlling cell proliferation are perturbed during ethanol exposure. Ethanol can induce the release of intracellular calcium stores, which stimulates the cell cycle, and it also up-regulates the expression of myc proteins associated with cell proliferation. Increased proliferation is advantageous during the preimplantation period, but ethanol interference with terminal differentiation events within developing tissues during organogenesis may underlie alcohol teratogenicity.

Application of magnetic resonance neurography in the evaluation of patients with peripheral nerve pathology.

Currently, diagnosis and management of disorders involving nerves are generally undertaken without images of the nerves themselves. The authors evaluated whether direct nerve images obtained using the new technique of magnetic resonance (MR) neurography could be used to make clinically important diagnostic distinctions that cannot be readily accomplished using existing methods. The authors obtained T2-weighted fast spin-echo fat-suppressed (chemical shift selection or inversion recovery) and T1-weighted images with planes parallel or transverse to the long axis of nerves using standard or phased-array coils in healthy volunteers and referred patients in 242 sessions. Longitudinal and cross-sectional fascicular images readily distinguished perineural from intraneural masses, thus predicting both resectability and requirement for intraoperative electrophysiological monitoring. Fascicle pattern and longitudinal anatomy firmly identified nerves and thus improved the safety of image-guided procedures. In severe trauma, MR neurography identified nerve discontinuity at the fascicular level preoperatively, thus verifying the need for surgical repair. Direct images readily demonstrated increased diameter in injured nerves and showed the linear extent and time course of image hyperintensity associated with nerve injury. These findings confirm and precisely localize focal nerve compressions, thus avoiding some exploratory surgery and allowing for smaller targeted exposures when surgery is indicated. Direct nerve imaging can demonstrate nerve continuity, distinguish intraneural from perineural masses, and localize nerve compressions prior to surgical exploration. Magnetic resonance neurography can add clinically useful diagnostic information in many situations in which physical examinations, electrodiagnostic tests, and existing image techniques are inconclusive.

Studies on type II progesterone receptor in MCF-7 cells.

These experiments demonstrate for the first time the existence of a Type II progesterone receptor (RpII) in MCF-7 human breast cancer cells. RpII was shown to have a lower affinity for tritiated progesterone ([3H]Pg) (Kd greater than or equal to 13 nM) than classical Rp (Kd less than or equal to 3 nM). RpII was detected by cytosolic, nuclear, and whole cell assays of MCF-7 cells. Scatchard analysis of [3H]Pg binding data revealed that classical Rp but not RpII could be recompartmentalized from the cytosolic to the nuclear pool by treating cells 1 h at 37 degrees C with 1 microM Pg. RpII levels were shown to be increased more than two-fold by growing MCF-7 cells for 4 days in 10 nM estradiol (E2) plus 100 nM Pg when compared to either untreated cells or to cells treated with only E2.

A second career in academic medicine.

Career changes in all vocations are relatively common in the forties age group due to a variety of factors which include a crisis period caused by polarities of Generativity versus Stagnation as conceptualized by Erik H. Erikson. Generativity is served not only by procreativity but also by guiding the next generation through teaching. The result can be the strength of Care. Stagnation can result in unhappiness, irrational and destructive behavior, or withdrawal. Concepts of young, old and mortality also come into focus. A successful career change from private practice to academic medicine depends upon a combination of power, opportunity, and character. To be successful, the change should be made for positive reasons and be based upon youthful concepts in the cold reality of the financial and intellectual challenges of a new and competitive career. If properly done, both the personal rewards and the contribution to future medical care can be quite positive.

Magnetic resonance neurography of the median nerve.

A magnetic resonance imaging sequence, combining fat and flow suppression with T2 weighting, has been used to produce high conspicuity images of the median nerve within the carpal tunnel. Standard maximum intensity projection techniques were then used to produce three-dimensional (3D) reconstructions of the nerve. Comparison of 3D projections with the wrist in a neutral position and wrist flexed at 45 degrees depicted changes in the shape and course of the median nerve through the carpal tunnel of normal volunteers. In some cases of carpal tunnel syndrome evidence of a localized compression was observed. A 3D image of a nerve may help in the diagnosis of peripheral neuropathy and be an aid to surgery of or near major nerves.

Alcohol inhibits neurite extension and increases N-myc and c-myc proteins.

Alcohol teratogenesis may be due, in part, to inhibition of neuronal differentiation by alcohol. Because decreases in the N-myc and c-myc proteins are believed to be linked causally to neuronal differentiation, we hypothesized that alcohol would increase N-myc and c-myc proteins in undifferentiated neuronal cells and would oppose the decreases in these two proteins that normally precede differentiation. In undifferentiated LA-N-5 cultured human neuroblastoma cells, alcohol increased N-myc protein levels (178% vs. control cells) and c-myc levels (222% of control). Retinoic acid decreased N-myc and c-myc and induced neurite outgrowth (a differentiation marker). Alcohol prevented retinoic acid-elicited decreases in both myc isoforms and prevented neurite outgrowth. A significant 100% increase in c-myc and an upward trend (48%) in N-myc were observed in CA1 pyramidal neurons of the dorsal hippocampus in mouse fetuses exposed prenatally to alcohol. These data suggest that increases in N-myc and c-myc protein levels are associated with inhibition of neurite extension by alcohol.

Alcohol reduces neurofilament protein levels in primary cultured hippocampal neurons.

High concentrations of alcohol (> or = 1.8%) were shown previously to impair health and viability of cultured hippocampal neurons. Because neurofilament proteins are essential for neuronal process outgrowth and differentiation, the effects of alcohol on these proteins were determined in the neuronal processes of primary cultured gestational day 18 rat hippocampal neurons. At the relatively lower concentrations used in the present study, alcohol caused a concentration-dependent reduction (< or = 47%) in 68 and 200 kDa neurofilament proteins (p < 0.05). Alcohol caused a 32% downward trend in 160 kDa neurofilament protein levels. Alcohol up to 1% (72-h exposure) produced no obvious alterations in neurite extension or explant morphology, and there were no visual signs of cell death. The sensitive MTT dye reduction assay showed no biochemical evidence of decreased cell viability at < or = 0.5% alcohol. The 32-47% reductions in neurofilament protein levels in vitro may hold implications for later hippocampal neuronal differentiation events in animals prenatally exposed to alcohol.

Anesthesia technique for serving the pedicle of a tongue flap in the presence of a pharyngeal flap.

A technique is described for anesthesia while severing the pedicle of a tongue flap to the palate, in the presence of a pharyngeal flap.

Skin abnormalities of the back in diastematomyelia.

The presence of congenital skin abnormalities on the back may be associated with a serious underlying spinal anomaly, diastematomyelia. The significance of the progressive development of neurological deficits, due to the presence of a bony or cartilaginous spur in the spinal cord, is stressed. An awareness of this condition should lead to an early diagnosis with a neurological evaluation and, if necessary, prophylactic surgery before irreversible nerve damage develops.

Treatment of total loss of the Achilles tendon by skin flap cover without tendon repair.

We present two cases of conservative treatment of total loss of the Achilles tendon. In our opinion the functional result is acceptable, without tendon grafting. The action of the sural muscles is transmitted through scar underlying the pedicled flaps used to resurface the wounds.

Growth of the cleft lip following a triangular flap repair.

This study involves 50 children who had a triangular flap repair for unilateral cleft lip. They have been followed for 5 to 14 years by serial measurements, photographs, and clinical evaluation. During the first 5 years, the lips were designed to allow for future growth. The expected growth did not occur. During the second 5 years, the lip length was designed equal to the normal side with the belief that unequal growth does not occur. In this group, the results supported the premise that deviation from the correct lip length would now be equally divided between too long and too short. None of the entire group has a lip which started too short becoming equal or starting equal to become too long. It is the conclusion of the authors that a repaired unilateral cleft lip retains the configuration and length determined at the time of the initial repair.