Pharmacological analysis of established ventricular fibrillation.

1. The effects of anti-arrhythmic drugs on the power spectrum of established ventricular fibrillation induced by endocardial electrical stimulation, have been studied in greyhounds anaesthetized with sodium pentobarbitone (35 mg kg-1, i.v.). 2. In dogs receiving no drug, initial recording of ventricular fibrillation showed a dominant frequency of 9.9 +/- 0.7 Hz (lead II) and 10.0 +/- 0.6 Hz (endocardium). After 3.3 min the frequency had fallen to 4.0 +/- 0.4 Hz in lead II, but remained high in the endocardium (10.7 +/- 0.5 Hz). 3. Lignocaine significantly reduced the dominant frequency for fibrillation recorded from lead II at (0-80 s), and for endocardial fibrillation at (0-200 s). 4. Pretreatment with propranolol or bretylium had little effect on the time course of the dominant frequency of fibrillation in lead II or the endocardium. 5. Verapamil prevented the fall in frequency seen in lead II after 80 s in the no drug group. A significantly higher frequency was maintained in both lead II (14.7 +/- 0.9 Hz) and the endocardium (14.8 +/- 0.9 Hz) for 3.3 min, compared with the no drug group (P less than 0.01). 6. Activation of fast sodium channels may determine the rapid frequency of the initial stages of ventricular fibrillation. The rapid fall in dominant frequency in lead II after fibrillation for 80 s can be prevented by calcium channel blockade and may be due to intracellular accumulation of calcium.     

Complex Genetic Disease: Can Genetic Strategies in Alzheimer's Disease and New Genetic Mechanisms Be Applied to Epilepsy?

Summary: Strategies used in molecular genetics have changed modern neurology. The gene or genes responsible for several major neurologic diseases have now been identified using "reverse" or positional genetics. Unexpected new genetic mechanisms have been discovered in human neurologic diseases, including (a) identical mutations of the prion protein gene in Creutzfeldt-Jakob disease and fatal familial insomnia with the phenotypic expression directed by an accompanying polymorphism; (b) stable duplications of chromosome 17 in Charcot-Marie-Tooth disease (type 1 A) that involve many genes, only one of which appears to cause neuropathy; and (c) highly variable, dynamic mutations in myotonic dystrophy, fragile X syndrome, and Kennedy's syndrome that modulate variable expressivity in multiple tissues. There is growing recognition that neurologic diseases are often complex genetic diseases with multifactorial rather than simple modes of inheritance. For example, genetic association/linkage strategies have interacted with biochemistry and immunopathology studies to produce new insights into the disease mechanism of late-onset Alzheimer's disease. The role of apolipoprotein E in late-onset Alzheimer's disease is an example of how new analytical techniques of genetic disease can be applied to dissect multiple genes. Similar research strategies are suggested for the study of epilepsy as a complex disease.     

Manipulation of intracellular calcium affects in vitro juvenile hormone synthesis by larval corpora allata of Manduca sexta.

The effect of altering intracellular free Ca2+ on juvenile hormone (JH) and acid synthesis by larval and pupally-committed corpora allata (CA) of fifth stadium Manduca sexta was investigated. Larval CA required extracellular Ca2+ greater than or equal to 0.1 mM for maximal JH synthesis, while JH acid synthesis by glands after pupal commitment was independent of extracellular Ca2+. Free Ca2+ in the hemolymph ranged from 1.4 to 2.1 mM during the fifth stadium. Both calcium ionophores and caffeine, which releases Ca2+ from intracellular stores, inhibited JH synthesis by larval CA but stimulated JH acid synthesis by post-commitment CA. These results suggest that intracellular stores may be the principal source of Ca2+ for the biosynthetic activity of the post-commitment gland. Calcium channel blockers (La3+, Cd2+) and antagonists (verapamil, isradipine and nitrendipine) decreased both JH and JH acid synthesis, indicating the existence of Ca2+ channels in the CA cell membrane. Calmodulin (CaM) antagonists inhibited the activity of both larval and post-commitment CA, suggesting an integral relationship of CaM to the effects of Ca2+ on gland activity. One of these effects is the demonstrated requirement of 0.1 mM extracellular Ca2+ for allatostatin inhibition of JH I synthesis by larval CA.     

MEASUREMENTS OF INTERFACE PRESSURE BETWEEN BODY SITES AND THE SURFACES OF FOUR SPECIALISED AIR MATTRESSES

SUMMARY Four specialised air mattresses had interface pressure measured under six body sites prone to pressure sores in 10 subjects, supine and sitting. The mattresses were the Clinirest (SSI) and FirstStep (KCI) continuous airflow mattress overlays, and Airwave (Pegasus) and Nimbus (Huntleigh) alternating pressure air mattresses. On the mattress overlays, average supine interface pressures were 2.33 kPa (scapula), 4.15 kPa (elbow), 1.94 kPa (sacrum) and 2.79 kPa (buttock), although they were higher at the occiput (7.97 kPa) and heel (11.7 kPa). The alternating pressure air mattresses had an average minimum interface pressure close to zero for three sites, rising to 4.28 kPa under the heel. Average maximum interface pressures were 8.61 kPa (occiput), 5.21 kPa (scapula), 4.90 (elbow), 4.85 kPa (sacrum), 4.61 kPa (buttock) and 13.2 kPa (heel). No accepted scientific method exists for comparing the two types of mattress. Our data suggest a clinical benefit at the occiput and heel (supine) in using an alternating pressure air mattress and a benefit in using a continuous airflow mattress overlay at other sites.     

Long-Term Subdural Strip Electrocorticographic Monitoring of Ictal Déjà Vu

Summary: We report a series of 8 patients with ictal déjà vu. Subdural strip electrocorticographic (ECoG) monitoring localized the ictal epileptogenic focus as follows: right (n = 6) and left (n = 2) mesiotemporal lobe. In all 8 patients, the left hemisphere was dominant for language function based on intracarotid amytal testing. In 6 right-handed patients, ictal déjà vu was associated with a right temporal lobe focus. However, in the 2 left-handed patients, the ictal focus was left temporal lobe. Although ictal déjà vu localizes the epileptic focus to temporal lobe, this experiential phenomenon appears to lateralize to the hemisphere nondominant for handedness.     

An evaluation of causes for unreliability of synaptic transmission.

Transmission at individual synaptic contacts on CA1 hippocampal pyramidal neurons has been found to be very unreliable, with greater than half of the arriving presynaptic nerve impulses failing to evoke a postsynaptic response. This conclusion has been reached using the method of minimal stimulation of Schaffer collaterals and whole cell recording in hippocampal slices; with minimal stimulation only one or a few synapses are activated on the target neuron and the behavior of individual synapses can be examined. Four sources for the unreliability of synaptic transmission have been investigated: (i) the fluctuation of axon thresholds at the site of stimulation causing the failure to generate a nerve impulse in the appropriate Schaffer collaterals, (ii) the failure of nerve impulses generated at the site of stimulation to arrive at the synapse because of conduction failures at axon branch points, (iii) an artifactual synaptic unreliability due to performing experiments in vitro at temperatures well below the normal mammalian body temperature, and (iv) transmission failures due to probabilistic release mechanisms at synapses with a very low capacity to release transmitter. We eliminate the first three causes as significant contributions and conclude that probabilistic release mechanisms at low capacity synapses are the main cause of unreliability of synaptic transmission.     

以双蒂腹壁下动脉穿支皮瓣再造乳房

目的 报道对有纵形剖腹产瘢痕的乳腺癌根治术后所造成的胸壁畸形，应用双蒂腹壁下动脉穿支皮瓣再造乳房的临床效果，从而说明胸廓内动脉远心端供血的可靠性。方法 应用游离的双侧腹壁下动静脉为蒂的腹壁下动脉穿支皮瓣与胸廓内动、静脉远近心断端分别进行端端吻合再造乳房4例。结果 临床应用4例，皮瓣全部成活，再造乳房的形态较满意。术后随访l0～26个月，无腹部薄弱或腹壁疝等并发症发生。结论 胸廓内动、静脉可提供远近心端两组可靠的受区血管。以双侧腹壁下动、静脉为蒂的横行腹壁下动脉穿支皮瓣，适用于乳腺癌根治术后的乳房再造，特别适用于有纵形剖腹产瘢痕及腹壁较薄者的整形修复。     

Cholecystokinin and neuropeptide Y receptors on single rabbit vagal afferent ganglion neurons: site of prejunctional modulation of visceral sensory neurons

A [¹²⁵I]cholecystokinin (CCK) analog and [¹²⁵I]peptide YY (PYY) were used to localize and characterize CCK and neuropeptide Y (NPY) receptor binding sites in the rabbit vagal afferent (nodose) ganglion. High concentrations of CCK and NPY binding sites were observed in 10.6% and 9.2% of the nodose ganglion neurons, respectively. Pharmacological experiments using CCK or NPY analogs suggest that both subtypes of CCK (CCK-A and CCK-B) and NPY (Y1 and Y2) receptor binding sites are expressed by discrete populations of neurons in the nodose ganglion. These results suggest sites at which CCK or NPY, released in either the nucleus of the solitary tract or a peripheral tissue, may modulate the release of neurotransmitters from a select population of visceral primary afferent neurons. Possible functions mediated by these receptors include modulation of satiety, opiate analgesia, and the development of morphine tolerance.