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Biomedical subjects

J A White

Publications and source records attributed to J A White.

At least 37 records · Page 2Linked to original sources

The Ross operation in a Jehovah's Witness: a paradigm for heart surgery in children without transfusion.

A 3-year-old 18 kg male child of the Jehovah's Witness faith presented with severe aortic regurgitation. A successful Ross procedure was performed using a pulmonary autograft, without the use of blood or blood product transfusion. Blood conservation strategy included: (1) preoperative treatment with recombinant human erythropoietin; (2) intraoperative strategies, including technical modifications to the Ross procedure, and the prophylactic use of fibrin glue; (3) utilization of a heparin-bonded cardiopulmonary bypass circuit and assisted venous drainage; and 4) the use of prebypass phlebotomy, cell-saving device and autotransfusion. The patient was discharged home on postoperative day 7 with a hemoglobin level of 11.9.

Aortic Valve Insufficiency↗

Minimally invasive resection of congenital subaortic stenosis.

Fifteen consecutive patients with membranous subaortic stenosis underwent resection by a minimal-access approach through a partial upper sternotomy using a cardioscope. There were no operative deaths and no postoperative complications. Twelve patients (80%) were extubated in the operating room. The mean hospital stay was 3.1 days, and 3 patients (20%) needed blood products. Our experience demonstrates that this modified approach is a safe and effective surgical option for resection of subaortic stenosis.

Adolescent↗

Cosgrove-Edwards Annuloplasty System: midterm results.

BACKGROUND: The Cosgrove-Edwards Annuloplasty System includes a universally flexible band that corrects mitral annular dilatation via measured plication of the posterior annulus. The purpose of this study was to evaluate midterm clinical and functional results in the first 197 patients receiving this flexible annuloplasty band at mitral valve repair. METHODS: From February 1993 to July 1994, 197 consecutive patients with mitral regurgitation had mitral valve repair using this system. Valve disease was degenerative in 73%, rheumatic in 15%, ischemic in 5%, infectious in 2.5%, and other in 4%. RESULTS: Immediately after repair, echocardiographic mitral regurgitation was none or trivial in 92%, 1+ in 5%, and 2+ in 3%. There were no hospital deaths. Late follow-up was available in 195 patients (99%), with 661 patient-years of follow-up available for analysis. Four-year actuarial survival was 93%, freedom from thromboembolism 94%, from endocarditis 98%, and from reoperation 95%. At a mean interval of 18 months, echocardiography in 157 patients demonstrated no or trace mitral regurgitation in 56%, 1+ in 24%, 2+ in 9%, 3+ in 6%, and 4+ in 3%. At a mean of 61 +/- 5 months, reconstruction of the mitral annulus from real-time three-dimensional echocardiographic images in 10 patients confirmed preserved nonplanar shape and sphincter mechanism of the mitral annulus. Annular orifice area decreased 28% +/- 11% during the cardiac cycle from a mean of 10.1 +/- 3.9 cm2 in diastole to 7.2 +/- 2.8 cm2 in systole. CONCLUSIONS: This annuloplasty system is effective for repair of mitral regurgitation secondary to all causes and preserves mitral annular flexibility and function at 5-year follow-up.

Female↗

Channel noise in neurons.

The probabilistic gating of voltage-dependent ion channels is a source of electrical 'channel noise' in neurons. This noise has long been implicated in limiting the reliability (repeatability) of neuronal responses to repeated presentations of identical stimuli. More recently, it has been shown to increase the range of spiking behaviors exhibited in some neural populations. Channel numbers are tied to metabolic efficiency and the stability of resting potential, and channel noise might be exploited by future cochlear implants in order to improve the temporal representation of sound.

Action Potentials↗

Pattern of degeneration of the spiral ganglion cell and its processes in the C57BL/6J mouse.

Although degeneration of spiral ganglion cells has been described as a histopathologic correlate of hearing loss both in animals and humans, the pattern and sequence of this degeneration remain controversial. Degeneration of hair cells and of spiral ganglion cells and their dendritic processes was evaluated in the C57BL/6J mouse, in which there is a genetically determined progressive sensorineural loss starting in the high frequencies that is similar to the pattern commonly seen in the human. Auditory function was evaluated by brainstem evoked responses, and degeneration of hair cells, ganglion cells and their dendrites was evaluated histologically at 3, 8, 12 and 18 months of age. Progressive loss of auditory sensitivity was correlated with the loss of outer and inner hair cells and spiral ganglion cells and their dendritic processes. In addition, dendritic counts were consistently lower at a distal location in the osseous spiral lamina (i.e. near the organ of Corti) than at a proximal location (i.e. near the spiral ganglion), and the difference between the number of distal dendrites and the number of proximal dendrites tended to be greater with advancing age. These observations suggest an age-related progressive retrograde degeneration of spiral ganglion cells. Thus, in degenerating cochleas, some remaining spiral ganglion cells may have no distal dendritic processes near the organ of Corti. This may have implications for successful stimulation of the cochlear neuron in cochlear implantation.

Age Factors↗

Nonhypoglycemic drug reactions of agents used to treat diabetes.

The different classes of agents now available for the treatment of diabetes, each with its own unique mechanism of action, present the clinician with numerous choices to achieve glycemic control. Therapy can be tailored for each patient. If the primary problem is insulin resistance, a thiazolidinedione can be used. The clinician should remember the potential adverse reactions of the drugs and their potential interaction with other conditions a patient may have. After this careful consideration, the optimal therapeutic regimen for a patient can be developed.

Benzamides↗

Interactions between distinct GABA(A) circuits in hippocampus.

Synchronous activity among synaptically connected interneurons is thought to organize temporal patterns such as gamma and theta rhythms in cortical circuits. Interactions between distinct interneuron circuits may underlie more complex patterns, such as nested rhythms. Here, we demonstrate such an interaction between two groups of CA1 interneurons, GABA(A,slow) and GABA(A,fast) cells, that may contribute to theta and gamma rhythms, respectively. Stratum lacunosum-moleculare (SL-M) stimuli that activate GABA(A,slow) inhibitory postsynaptic currents (IPSCs) in pyramidal cells simultaneously depress the rate and amplitude of spontaneous GABA(A,fast) IPSCs for several hundred milliseconds. This suppression has a similar pharmacological profile to GABA(A,slow) IPSCs, and SL-M stimuli elicit GABA(A,slow) IPSCs in interneurons. We conclude that GABA(A,slow) cells inhibit both pyramidal cells and GABA(A,fast) interneurons and postulate that this interaction contributes to nested theta/gamma rhythms in hippocampus.

Animals↗

Isolated bypass grafting of the left internal thoracic artery to the left anterior descending coronary artery: late consequences of incomplete revascularization.

OBJECTIVE: Multiple strategies to achieve some degree of myocardial revascularization are available. In some, less complete revascularization is accepted to limit invasiveness. To examine the issues of incomplete revascularization, we assessed the long-term impact of additional non-left anterior descending coronary artery stenoses in patients undergoing only grafting of the left internal thoracic artery to the left anterior descending coronary artery. METHODS: A total of 2067 patients underwent primary isolated grafting of the left internal thoracic artery to the left anterior descending coronary artery from 1971 to 1997. Of these, 26% and 13% had 2- and 3-system disease, respectively. Multivariable analyses of survival and reintervention were performed in the hazard function domain for 27,683 patient-years of follow-up (mean 14 +/- 6.7). RESULTS: Survival was 99%, 88%, and 62% at 1, 10, and 20 years. Right coronary artery or left circumflex system disease of 50% or more (P =.02) and particularly high-grade (>/=70%) left circumflex (P =.01) and proximal right coronary artery disease (P =.01), as well as any degree of left main trunk stenosis (P <.0001), were associated with reduced long-term survival. Compared with 75% 20-year survival in patients with no non-left anterior descending disease, those with either left circumflex or left main trunk disease experienced a 44% survival, and those with proximal right coronary artery disease, 42%. The most common stated reason for incomplete revascularization was small vessel size. Freedom from reintervention was 89% and 65% at 10 and 20 years, respectively. High-grade left main trunk disease, but, in contrast, mid or distal disease of the right coronary artery, and not left circumflex disease, were risk factors for reintervention. CONCLUSIONS: These findings call into question the long-term appropriateness of interventions whose strategy includes leaving unrevascularized segments in territories not in the distribution of the left anterior descending coronary artery.

Adult↗

A new set of Arabidopsis expressed sequence tags from developing seeds. The metabolic pathway from carbohydrates to seed oil.

Large-scale single-pass sequencing of cDNAs from different plants has provided an extensive reservoir for the cloning of genes, the evaluation of tissue-specific gene expression, markers for map-based cloning, and the annotation of genomic sequences. Although as of January 2000 GenBank contained over 220,000 entries of expressed sequence tags (ESTs) from plants, most publicly available plant ESTs are derived from vegetative tissues and relatively few ESTs are specifically derived from developing seeds. However, important morphogenetic processes are exclusively associated with seed and embryo development and the metabolism of seeds is tailored toward the accumulation of economically valuable storage compounds such as oil. Here we describe a new set of ESTs from Arabidopsis, which has been derived from 5- to 13-d-old immature seeds. Close to 28,000 cDNAs have been screened by DNA/DNA hybridization and approximately 10,500 new Arabidopsis ESTs have been generated and analyzed using different bioinformatics tools. Approximately 40% of the ESTs currently have no match in dbEST, suggesting many represent mRNAs derived from genes that are specifically expressed in seeds. Although these data can be mined with many different biological questions in mind, this study emphasizes the import of photosynthate into developing embryos, its conversion into seed oil, and the regulation of this pathway.

Arabidopsis↗

Acute injury incidence in professional county club cricket players (1985-1995).

BACKGROUND: There is a dearth of evidenced based research into sports injury in professional cricket. AIM: To investigate the incidence, nature, and site of acute injuries sustained by professional cricketers at one English county club over the period 1985-1995. METHODS: Injuries in a sample of 54 cricketers who had played in the first team for the same county cricket club in any or all seasons between 1985 and 1995 were investigated. Injury was defined as the onset of pain or a disability resulting from either training for or playing cricket, which caused the player to seek medical attention. RESULTS: An acute injury rate of 57.4 injuries per 1000 days of cricket played was found, with most injuries sustained during April, the month in which the least number of days were played. The lower limb was the region most vulnerable to injury, accounting for 44.9% of all injuries, followed by the upper limb (29.4%), the trunk (20.0%), and the head and neck (5.7%). No significant difference in injury incidence among player positions was found. CONCLUSION: There is a need for a system of epidemiological data collection and development of a national cricket injury database to help predict, reduce, and prevent injury at all levels of the game.

Adult↗

Characterization of the rat type III hexokinase gene promoter. A functional octamer 1 motif is critical for basal promoter activity.

A 1532-base pair 5'-flanking region of the gene encoding rat type III hexokinase has been cloned and sequenced. The total sequence includes positions -1548 to -17 (A of the translational start ATG as position +1). Using luciferase reporter constructs transfected into PC12 (rat pheochromocytoma) and L2 (rat lung) cells, basal promoter activity has been associated with sequence between -182 and -89. This includes a single transcriptional start site, an adenine at position -134 identified by primer extension. Together with previously cloned cDNA sequence, this accounts for an mRNA of approximately 3.9 kilobases, found by Northern blotting of RNA from rat lung and kidney. Sequence upstream of the transcriptional start site was devoid of canonical TATA and CAAT elements. An octamer 1 (Oct-1) binding site, located between positions -166 and -159 was shown by deletion analysis and site-directed mutation to be critical for promoter activity. Nuclear extracts from PC12 cells contained a protein (or proteins) specifically binding the octamer sequence, and supershift experiments with anti-Oct-1 indicated involvement of this ubiquitously expressed transcription factor in the complex. Sequence including the Oct-1 site and immediately adjacent regions was protected from DNase I digestion in footprinting experiments with nuclear extracts from PC12 cells. Reverse transcription polymerase chain reaction indicated that levels of type III hexokinase mRNA in rat tissues increased in the order brain < liver < lung approximately kidney; immunoblotting indicated that type III hexokinase protein in these tissues increased in a similar manner.

Animals↗

Identification, functional characterization, and chromosomal localization of USP15, a novel human ubiquitin-specific protease related to the UNP oncoprotein, and a systematic nomenclature for human ubiquitin-specific proteases.

We have identified a novel gene, USP15, encoding a human ubiquitin-specific protease (USP). The USP15 protein consists of 952 amino acids with a predicted molecular mass of 109.2 kDa and contains the highly conserved Cys and His boxes present in all members of the UBP family of deubiquitinating enzymes. USP15 shares 60.5% sequence identity and 76% sequence similarity with the human homolog (UNP/Unph/USP4) of the mouse Unp proto-oncogene. Recombinant USP15 demonstrated ubiquitin-specific protease activity against engineered linear fusions of ubiquitin to beta-galactosidase and glutathione S-transferase. USP15 can also cleave the ubiquitin-proline bond, a property previously unique to Unp/UNP. Chromosomal mapping by fluorescence in situ hybridization and radiation hybrid analyses localized the USP15 gene to chromosome band 12q14, a different location than that of UNP (3p21.3). Analysis of expressed sequence tag databases reveals evidence of alternate polyadenylation sites in the USP15 gene and also indicates that the gene may possess an exon/intron structure similar to that of the Unp gene, suggesting they have descended from a common ancestor. A systematic nomenclature for the human USPs is proposed.

Amino Acid Sequence↗

AND and AND-OR drug mixture discriminations in rats: generalization to single drugs and drug mixtures.

RATIONALE: Studies of the discriminative stimulus effects of drug mixtures provide an approach to polydrug abuse and studies on single drugs with multiple effects. OBJECTIVE: This study was designed to investigate whether the use of the AND-OR procedure increases the specificity of drug mixture discriminations. METHODS: Rats were trained to discriminate a mixture of amphetamine (0.4 mg/kg) plus pentobarbitone (10 mg/kg) from saline (AND-discrimination, n = 8) or to discriminate the same mixture from its component drugs alone (AND-OR discrimination, n = 9). The studies used two-lever operant procedures with a tandem variable interval 1-min fixed ratio 10 schedule of food reinforcement. RESULTS: Under AND-discrimination conditions, there was partial generalization to nicotine and midazolam when each drug was administered singly, and there was no generalization to cocaine, caffeine or ethanol. With the AND-OR discrimination, there was no generalization to any of the preceding drugs administered singly. In "single substitution" tests, nicotine or midazolam was co-administered with the training doses of pentobarbitone and amphetamine, respectively; there was full generalization in the AND-discrimination and partial generalization under AND-OR conditions. Cocaine co-administered with pentobarbitone generalized fully under both procedures, but the dose of cocaine needed was much larger in the AND-OR than in the AND-discrimination. In "dual substitution" tests, mixtures of two novel substances were tested. Mixtures of either nicotine plus midazolam or caffeine plus ethanol produced very marked generalization under AND-discrimination conditions, but were without significant effect in the AND-OR procedure. Throughout the studies, in every instance where comparisons were made, generalization was greater or occurred at lower doses under AND- than under the AND-OR discrimination. CONCLUSIONS: The study yielded extensive evidence supporting the hypothesis that the AND-OR discrimination procedure increases the specificity of discriminations based on drug mixtures.

Animals↗

Dural waisting as a sign of subarachnoid extension of cavernous carotid aneurysms: a follow-up case report.

OBJECTIVE: Even when augmented by CT and MRI, it can be difficult on angiography to predict which intracavernous carotid artery aneurysms (ICCAA) have subarachnoid extension and therefore pose a higher risk of subarachnoid hemorrhage. Previously we reported a case of an ICCAA, which on angiogram had a focal tapering of the dome that we termed a "waist." At surgery this lesion was found to have subarachnoid extension. We postulated that this dural "waisting" on the arteriogram was a predictor of subarachnoid extension. Herein we report a second case of an ICCAA with the angiographic appearance of a waist that was also confirmed to have subarachnoid extension at surgery, thereby strengthening our original hypothesis. CLINICAL PRESENTATION: A 40-year-old woman presented with a 3-month history of bitemporal headache, diplopia, and a left sixth nerve palsy. MRI showed a lesion in the vicinity of the left cavernous carotid sinus and an arteriogram confirmed the presence of a large cavernous carotid aneurysm. As in the previous case, the aneurysm fundus was indented, creating a waist on the aneurysm dome. INTERVENTION: After passing a trial balloon occlusion of the involved carotid artery, the patient was brought to the operating room for lesion trapping. The aneurysm fundus was seen to extend beyond the falciform ligament and with subsequent dissection, the neck of the aneurysm was seen to incorporate the carotid artery distal to the ophthalmic artery. The aneurysm was trapped by ligating the internal carotid artery in the neck and by placing a clip on the intracranial carotid proximal to the posterior communicating artery. CONCLUSION: The presence of subarachnoid extension of an ICCAA can be difficult to elucidate on an arteriogram. This is an additional case in which a focal narrowing or "waisting" of the aneurysm dome seen on an angiogram served as a marker of subarachnoid extension.

Adult↗

Drug mixtures and ethanol as compound internal stimuli.

Drug discrimination methods that entail training with mixtures of drugs may shed light on polydrug abuse and on the actions of single drugs that interact with more than one receptor. In AND-discrimination procedures (drug A + drug B vs. vehicle), mixtures are discriminated primarily on the basis of their component drugs: these discriminations may be useful for testing interactions between component drugs in mixtures. The role of training dose, overshadowing and associative blocking in AND-discriminations have been investigated. For example, after prior training with midazolam, it was possible to demonstrate associative blocking of the nicotine element of the mixture stimulus, and vice versa. Using the AND-OR discriminations (drug A + drug B vs. drug A or drug B) increased pharmacological specificity considerably, and these procedures may be valuable for determining whether the effects of a novel mixture are similar to the combined effects of the training drugs. Ethanol is an example of a single drug that may produce a compound cue; rats trained to discriminate ethanol from water generalize (asymmetrically) to GABA(A) enhancers such as chlordiazepoxide (CDP) or pentobarbitone, to NMDA antagonists such as dizocilpine (MK-801), and to some serotonin agonists, such as trifluoromethylphenylpiperazine (5-HT(1B/2C)). In addition, rats trained to discriminate mixtures of either CDP or pentobarbitone plus MK-801 generalize to ethanol. A previous history of training with MK-801 or CDP (prior to ethanol discrimination training) enhanced the MK-801-like and CDP-like effects of ethanol respectively, but associative blocking of proposed elements in the ethanol stimulus was not seen. These studies provide some support for the multielement concept of ethanol discrimination but also suggest that rules governing three-component stimuli (such as those putatively produced by ethanol) may differ from those for the two-component mixtures of drugs studied previously.

Animals↗

Influence of training paradigm on specificity of drug mixture discriminations.

Generalization to different drugs and drug mixtures has been examined in rats trained to discriminate a mixture of amphetamine (0.4 mg/kg) plus pentobarbitone (10 mg/kg) from saline (AND discrimination, n = 8) or to discriminate the same mixture from its component drugs alone (AND-OR discrimination, n = 9). The studies used two-lever operant procedures with a tandem variable interval 1-min fixed-ratio 10 schedule of food reinforcement. There was partial generalization to nicotine and midazolam and no generalization to cocaine, caffeine, or ethanol under AND-discrimination conditions and no generalization to any of these drugs in the AND-OR discrimination. Nicotine or midazolam coadministered with the training doses of pentobarbitone and amphetamine, respectively, produced full generalization in the AND discrimination and partial generalization under AND-OR conditions. Cocaine coadministered with pentobarbitone generalized fully under both procedures, but at larger doses in the AND-OR than in the AND discrimination. Mixtures of either nicotine plus midazolam or caffeine plus ethanol produced very marked generalization under AND-discrimination conditions, but were without significant effect in the AND-OR procedure. The results consistently supported the hypothesis that the AND-OR discrimination procedure increases the specificity of discriminations based on drug mixtures.

Animals↗

Predicting coronary disease risk based on short-term RR interval measurements: a neural network approach.

Coronary heart disease is a multifactorial disease and it remains the most common cause of death in many countries. Heart rate variability has been used for non-invasive measurement of parasympathetic activity and prediction of cardiac death. Patterns of heart rate variability associated with respiratory sinus arrhythmia have recently been considered as possible indicators of coronary heart disease risk in asymptomatic subjects. The aim of this work is to detect individuals at varying risk of coronary heart disease based on short-term heart rate variability measurements under controlled respiration. Artificial neural networks are used to recognise Poincaré-plot-encoded heart rate variability patterns related to coronary heart disease risk. The results indicate a relatively coarse binary representation of Poincaré plots could be superior to an analogue encoding which, in principle, carries more information.

Coronary Disease↗