PubMed Health⌕ Search

Biomedical subjects

C Adams

Publications and source records attributed to C Adams.

At least 91 records · Page 5Linked to original sources

Alzheimer's disease research: a game of connect the dots.

Although a vast number of experimental investigations have focused on various aspects of Alzheimer's disease (AD), the pathogenic mechanism of the disease has not been established. AD research is a dynamically changing field that has entertained a variety of hypotheses. Since most of the data pertaining to AD pathogenesis is obtained in postmortem tissue or in vitro experiments, researchers must play a game of 'connect the dots' to try to correlate the diverse aspects of the disease and generate hypotheses regarding the sequence of pathological events. This article reviews the current state of AD research, and presents three hypothetical models for disease progression.

Alzheimer Disease↗

Clinical and molecular analysis of a pedigree of southern Italian ancestry with spinocerebellar ataxia type 2.

We describe patients from five generations of a pedigree with mutations in the spinocerebellar ataxia type 2 gene (SCA2). The predominant clinical features observed included both appendicular and truncal ataxia, dysarthria, slowness of saccades, and impaired optokinetic responses. Successive generations demonstrated both earlier ages of onset as well as increasing numbers of trinucleotide repeat sequences. The signs found in this family are compared with the description of other families with SCA2 as well as with other types of dominantly inherited spinocerebellar ataxias.

Adolescent↗

Cyclosporin treatment of perianal fistulas in dogs.

The purpose of this pilot study was to investigate the efficacy of cyclosporin in treating perianal fistulas (PAF) in dogs. Based on resolution of all fistulas in all dogs with remission times up to > 18 months, we conclude that cyclosporin therapy is the treatment of choice for PAF in dogs.

Animals↗

[Calculation of the regurgitation fraction in mitral insufficiency by Doppler echocardiography using a study of the zone of flow convergence].

The aim of this study was to propose a new method for calculating the regurgitation fraction of mitral insufficiency by the proximal isovelocity surface area (PISA) method and to compare it with the value of the catheter regurgitation fraction. Thirty-five patients (21 men and 14 women) aged 59 +/- 13 years with isolated mitral insufficiency were studied. Analysis of the proximal isovelocity surface area enabled calculation of an instantaneous maximum regurgitant flow, surface of the regurgitant orifice and the regurgitant volume. The regurgitant fraction was calculated by dividing the regurgitant volume by the sum of the regurgitant volume and aortic stroke volume measured by Doppler echocardiography. These parameters were compared with the corresponding catheter data and the angiographic grade of mitral insufficiency. The echocardiographic and catheter studies were performed within 1.7 +/- 1.2 days. There was a statistically significant correlation between the instantaneous maximum regurgitant flow calculated by the PISA method and the catheter regurgitant flow (r = 0.88; p = 0.0001); between the regurgitant volume calculated by the PISA method and the catheter regurgitant volume (r = 0.85; p = 0.0001) and the regurgitation fraction calculated by the PISA method and the catheter regurgitant fraction (r = 0.82; p = 0.0001). A regurgitant fraction by the PISA method of > 45% corresponded to severe mitral regurgitation (> or = angiographic grade 3 and/or a catheter regurgitant fraction > or = 50%) with a sensitivity of 88% and a specificity of 100%. The PISA method should form part or routine quantification of mitral insufficiency.

Adult↗

Expression of insulin-like growth factor-1 (IGF-1) and IGF-binding protein 2 (IGF-BP2) in the hippocampus following cytotoxic lesion of the dentate gyrus.

Receptor binding and gene expression of several members of the IGF gene family were examined in the rat brain following lesion of the hippocampal dentate gyrus granular cells by intradentate colchicine injection. Dentate granular cell loss was accompanied by extensive reactive gliosis in the lesioned hippocampus and damaged overlying cortex, as verified by the increase in GFAP mRNA and BS-1 lectin binding. At 4 days post-lesion, 125I-IGF-2 binding was dramatically increased within the lesioned dentate gyrus and damaged overlying cortex, and corresponded temporally and anatomically with increased IGF-BP2 gene expression following the lesion. Increased IGF-BP3 gene expression was only observed in the overlying cortex at 10 days post-lesion, and corresponded with an increase in 125I-IGF-1 binding at the injured surface of the cortex. Type-2 IGF receptor mRNA expression was reduced to background levels in the lesioned dentate gyrus, suggesting that IGF-BP2 was a major component of the observed increase in 125I-IGF-2 binding. In situ hybridization also revealed a prominent increase in IGF-1 mRNA expression by 4 days post-lesion, which was localized within the lesioned dentate gyrus and damaged cortical areas, and was shown to be expressed by microglia. While no IGF-2 mRNA expression was observed within the CNS, either prior to, or following the lesion, IGF-2 mRNA expression was observed in the choroid plexus, meningeal membranes, and in blood vessel endothelium, providing a potential source for the transport of IGF-2 into the CNS. In the injured CNS, increased IGF-BP2 expression may act to maintain or transport IGF-1 or IGF-2, as well as modulate the local autocrine and paracrine actions of the IGFs. Increased microglial IGF-1 expression following colchicine treatment correlates with the timing of a number of post-traumatic events within the CNS, suggesting that IGF-1 may have a role as a neuroprotectant for surviving neurons and signal for local neuronal sprouting, as well as a role in reactive astrogliosis.

Animals↗

Prospective evaluation of dynamic contrast enhanced magnetic resonance imaging in the evaluation of fistula in ano.

Forty-two patients with a suspected diagnosis of fistula in ano underwent prospective comparison of digital rectal examination, dynamic contrast enhanced magnetic resonance imaging (DCEMRI) and surgical exploration. There were five discordancies: DCEMRI showed an ischiorectal abscess and track with no enteric connection in one patients who at operation was found to have a well epithelialized primary fistula. Four patients with fistulas on DCEMRI had no enteric opening found at surgery and were treated as having sinuses. Long-term follow-up has shown failure to heal in all patients and further surgery confirmed missed fistula. Compared with final outcome measures DCEMRI had a sensitivity of 97 per cent and specificity of 100 per cent in the detection of fistula. DCEMRI also identified more secondary tracks and was more accurate at identifying complex fistulas than either digital rectal examination alone or surgical exploration.

Adult↗

Reduced transmitter release conferred by mutations in the slowpoke-encoded Ca2(+)-activated K+ channel gene of Drosophila.

Potassium channels control the repolarization of nerve terminals and thus play important roles in the control of synaptic transmission. Here we describe the effects of mutations in the slowpoke gene, which is the structural gene for a calcium activated potassium channel, on transmitter release at the neuromuscular junction in Drosophila melanogaster. Surprisingly, we find that the slowpoke mutant exhibits reduced transmitter release compared to normal. Similarly, the slowpoke mutation significantly suppresses the increased transmitter release conferred either by a mutation in Shaker or by application of 4-aminopyridine, which blocks the Shaker-encoded potassium channel at the Drosophila nerve terminal. Furthermore, the slowpoke mutation suppresses the striking increase in transmitter release that occurs following application of 4-aminopyridine to the ether a go-go mutant. This suppression is most likely the result of a reduction of Ca2+ influx into the nerve terminal in the slowpoke mutant. We hypothesize that the effects of the slowpoke mutation are indirect, perhaps resulting from increased Ca2+ channel inactivation, decreased Na+ or Ca2+ channel localization or gene expression, or by increases in the expression or activity of potassium channels distinct from slowpoke.

4-Aminopyridine↗

Regional gene expression of the glutamate receptor subtypes GluR1, GluR2, and GluR3 in human postmortem brain.

Although glutamatergic receptors are localized throughout the mammalian central nervous system (CNS), the specific cellular localization of the various glutamatergic receptor subtypes throughout human brain remains largely unknown. PCR fragments to human GluR1, GluR2, and GluR3 receptor subtypes were cloned and used as probes for in situ hybridization in order to examine the anatomical and cellular localization of glutamate receptor subtype gene expression in dissected regions of human postmortem brain tissue. Although hybridization was observed throughout the CNS, results indicated that the highest levels of hybridization were in the hippocampus, with localization primarily to cells in the pyramidal cell layer of the CA1-CA3 region, and the granular cells of the dentate gyrus. Prominent hybridization also was observed in the medium to large neurons of the cingulate cortex, temporal lobe, septum, and amygdala, as well as in scattered neurons in the thalamus, cerebral cortex, and medulla. A striking pattern of differential hybridization was observed within the cerebellum. GluR1 demonstrated light hybridization along the Purkinje/Bergmann glia layer, with GluR2 and GluR3 demonstrating hybridization to Purkinje cells, and GluR3 also to cells within the molecular layer, previously identified as stellate-basket cells. Changes in glutamate receptor function have been shown to be important in the pathogenesis of a number of neurological disorders. Therefore, an examination of glutamatergic receptor expression in human postmortem brain tissue may provide important information on the molecular basis of a variety of neurological and psychiatric disorders of the CNS.

Base Sequence↗

Middle cerebral artery dissection.

A 12-year-old girl had minor head trauma, with resultant mild headache, one day prior to onset of an apparently generalized tonic clonic seizure, right hemiparesis and dysphasia. A cranial CT scan showed evidence of a left middle cerebral artery infarct. Despite ventilation, fluid restriction, mannitol, thiopental infusion and intracranial pressure monitoring she deteriorated and died. Autopsy demonstrated dissection of the left middle cerebral artery with an intact internal carotid artery and no evidence of vasculitis. Middle cerebral artery dissection in children is very rare. Most reported cases are diagnosed at autopsy. The pathogenesis of cerebral artery dissection may include preceding minor head trauma or exertion and this should be sought for in the history.

Accidents, Home↗

Interaction between nutrition and Eimeria acervulina infection in broiler chickens: development of an experimental infection model.

In three experiments broiler chickens were inoculated with sporulated Eimeria acervulina oocysts at 18 d of age. Feed intake, body-weight gain, brush-border enzyme activities, fat digestion, protein digestion and protein retention were measured. Body-weight gain was reduced during the acute phase of the infection and increased during the recovery phase of the infection. Feed intake was decreased on day 4 and day 5 postinfection (PI) and increased from day 7 to day 11 PI. Maltase (EC 3.2.1.20) and sucrase (EC 3.2.1.48) activities were decreased on day 5 PI in all intestinal segments. In Expts 2 and 3, however, maltase activity was increased in the ileum. Fat digestion was decreased from day 2 to day 11 PI. N digestion and retention were decreased from day 2 to day 11 PI.

Animal Nutritional Physiological Phenomena↗

Interaction between nutrition and Eimeria acervulina infection in broiler chickens: diet compositions that improve fat digestion during Eimeria acervulina infection.

Previously an experimental infection model was developed in which broiler chickens were inoculated with sporulated Eimeria acervulina oocysts at an age of 18 d. The infection resulted in adverse performance results and reduced nutrient digestion. In two new experiments with the infection model effects of diet adjustments on fat digestion were investigated. In the first experiment addition of 0.4 g cholic acid/kg to a diet rich in animal fat resulted in increased fat digestion during the infection. In the second experiment replacing animal fat by coconut oil resulted in improved fat digestion during the coccidiosis infection. However, replacement of animal fat by soybean oil did not improve fat digestion.

Animal Nutritional Physiological Phenomena↗

Nicotinic receptor function in schizophrenia.

Schizophrenia can be partially characterized by deficits in sensory processing. Biochemical, molecular, and genetic studies of one such endophenotype, the P50 auditory-evoked potential gating deficit, suggest that one of the neuronal nicotinic receptors, the alpha 7 nicotinic receptor, may function in an inhibitory neuronal pathway involved in this phenotype. The P50 deficit is normalized in nongating subjects by nicotine. Although most schizophrenia patients are heavy smokers, the effects of nicotine may be transient, as alpha 7 receptors are known to desensitize rapidly. In an animal model of the P50 gating deficit, antagonists of the alpha 7 nicotinic receptor block normal gating of the second of paired auditory stimuli. Regional localization of receptor expression includes areas known to function in sensory filtering. An inhibitory mechanism, in the hippocampus, may involve nicotinic stimulation of gamma-aminobutyric acid (GABA)ergic interneurons, resulting in decreased response to repetitive stimuli. Expression of the alpha 7 receptor is decreased in hippocampal brain tissue, dissected postmortem, from schizophrenia subjects. The P50 deficit is inherited in schizophrenia pedigrees, but it is not sufficient for disease development and thus represents a predisposition factor. Linkage analysis between the P50 deficit in multiplex schizophrenia pedigrees and deoxyribonucleic acid (DNA) markers throughout the genome yielded positive lod scores to DNA markers mapping to a region of chromosome 15 containing the alpha 7 nicotinic receptor gene. Elucidation of possible interactions of the P50 with other factors, known to be important in the etiology of the disease, is important in determining an overall pathobiology of schizophrenia.

Animals↗

Contralateral cerebellar hemorrhagic infarction after pterional craniotomy: report of five cases and review of the literature.

OBJECTIVE AND IMPORTANCE: Five cases of cerebellar hemorrhagic infarction complicating pterional craniotomy are presented. Recognition of this rare complication may be delayed, with catastrophic consequences, because clinicians are unaware of the possibility. We suggest that the mechanism of this complication is dislocation of the dependent part of the cerebellum and venous obstruction causing hemorrhagic infarction. CLINICAL PRESENTATION: Five patients undergoing pterional craniotomies for benign conditions (four unruptured aneurysms and one meningioma) developed hemorrhagic infarction of the contralateral cerebellum in the postoperative period. This resulted in obstructive hydrocephalus and brain stem compression. A review of the literature revealed only one previous report of a similar complication in patients with gross coagulopathy. This was not a problem in our patients. INTERVENTION: The time of onset of symptoms varied from immediately postoperative to 24 hours later. Once the diagnosis was made, the hydrocephalus was drained and the posterior fossa was decompressed. CONCLUSION: The outcome depended on two variables: 1) the rate of development of hemorrhagic infarction and the associated complications and 2) the amount of time that elapsed before remedial action was taken. Two patients with the first signs of deterioration in the immediate postoperative period had the worst outcome; one died and the other remained severely disabled. In two patients with good neurological recovery, problems were identified and corrected within 4 hours of the first sign of deterioration. Rapid overdrainage of cerebrospinal fluid during supratentorial surgery should be avoided, and the fluid volume should be replaced before closure. Postoperative evaluation of patients whose conditions deteriorate after supratentorial craniotomy should include adequate imaging studies of the posterior fossa.

Cerebellar Diseases↗

Elevated aminotransferase activity as an indication of muscular dystrophy: case reports and review of the literature.

Five male children are reported in whom incidental recognition of elevated serum alanine aminotransferase (ALT) activity initiated investigation to identity the cause of suspected hepatocellular injury. All five were later diagnosed with X chromosome-linked muscular dystrophy. The serum level of ALT, generally considered to be specific for hepatocellular injury, was increased two to 25 times above normal in all the reported cases. Paradoxically, the increase in ALT activity was greater than that of serum aspartate aminotransferase (three to 16 times normal), an enzyme whose elevation is generally recognized as being less specific and indicative of muscle, cardiac, kidney, pancreatic, red blood cell or hepatic injury. At presentation to the gastrointestinal service, one case, age 2.5 months, had no symptoms or signs of neuromuscular dysfunction, while the other four had previously unrecognized hypertrophy of the calves, proximal limb weakness, positive Gower's sign or delayed gross motor skills. All five patients had marked elevation of serum creatine kinase activity and histopathologically confirmed muscular dystrophy. The practical clinical implication of this report is that children with elevated serum ALT, in the absence of other signs and symptoms of hepatic injury, may have occult muscular disease--most frequently muscular dystrophy. Although the clinical signs of muscular dystrophy may be subtle or absent, early determination of creatine kinase will suggest the correct diagnosis and minimize extensive and invasive investigation focusing on hepatic injury.

Adolescent↗

Dynamic contrast-enhanced MR imaging of perianal fistulas.

OBJECTIVE: The objective of this study was to prospectively compare dynamic contrast-enhanced MR imaging with MR sequences previously described for assessing perianal fistulas in order to determine the best MR protocol for their evaluation. SUBJECTS AND METHODS: MR examinations of 42 consecutive patients with clinically suspected perianal fistulas were independently evaluated by two experienced observers blinded to the findings of digital rectal examination. The observers' evaluations occurred before definitive surgical exploration. All patients had body-coil MR imaging examinations, including the following sequences that were ranked for anatomic and pathologic information: spin-echo T1-weighted, short inversion time inversion recovery, and dynamic contrast-enhanced MR imaging in the coronal plane; and spin-echo T2-weighted imaging in the axial plane. Surgical findings were accepted as the gold standard and were recorded independently by the surgeon, who was unaware of the findings of the MR assessment. MR findings were subsequently correlated with digital rectal examination before surgery and with clinical follow-up. RESULTS: MR imaging correctly allowed our blinded observers to predict the surgical anatomy of perianal disease in 37 of the 42 patients (accuracy, 88%). For detection of the presence and site of an enteric fistulous entry, MR imaging had a sensitivity of 97%, a specificity of 67%, a positive predictive value of 88%, and a negative predictive value of 89%. On MR imaging examination, eight patients had no fistula, 12 had simple intersphincteric fistulas, and 22 had complex fistulas. MR imaging revealed all 14 perianal abscesses and fluid collections found at surgery. Digital rectal examination before surgery failed to reveal abscesses or important secondary tracks in eight of the 22 complex fistulas. For anatomic and pathologic depiction of fistulas, dynamic contrast-enhanced MR imaging ranked as the best sequence for 22 of 34 fistulas. The short inversion time inversion recovery sequence, which was unable to distinguish small abscesses from perianal inflammation and showed spurious high signal in old fibrotic tracks, led our observers to misdiagnose five cases. In four patients for which initial surgery did not confirm enteric entry sites that our observers had predicted by MR imaging, follow-up has confirmed the observers' diagnoses. The observers' evaluations of the MR examinations agreed in 37 (88%) of the 42 cases. CONCLUSION: MR imaging is more accurate than digital rectal examination before surgery in detecting complex features of perianal fistulas. MR imaging is noninvasive, is highly accurate, and has low interobserver variability. With MR imaging, observers may better predict outcome than with initial surgical exploration. MR assessment that includes dynamic contrast-enhanced MR imaging and axial T2-weighted sequences (examination time, 20 min) provides the anatomic and pathologic information required to guide surgical management.

Adult↗