Carcinoma of the penis metastasizing to the dorsal spine. A case report

Carcinoma of the penis tends to have a predictable route of spread by direct invasion and by regional lymphatic involvement to the inguinal group of lymph nodes. Blood-borne distant spread is rare, last to occur, and is seen in 1-3% of cases. Metastasis to the spine is even rarer. We encountered one such case who presented with spinal metastasis, as documented by the whole body bone scan, and this was later followed by involvement of the inguinal nodes. This case is unique in its site of metastatic presentation as well as its pattern of presentation.     

Bioprosthetic heart valves--replacing order with chaos: electron microscopic study

Rheumatic heart disease is a significant clinical entity in young children, especially in the developing world. One of the major long-term effects of ill managed rheumatic fever is irreversible damage to the cardiac valve leaflets, primarily on the left side. With the limited success of currently available mechanical and bioprosthetic valves, there is an urgent need for new directions in bioprosthetic valves, both in material, including source, degree of fixation, surface, bulk modifications, etc., and design. In the present paper, new proposals in the material selection and fabrication of bioprosthetic valves are proposed based on electron microscopic studies of natural valve leaflets and the pericardial surface. Current approaches for bioprosthetic valve fabrications include the wide use of the pericardium as a leaflet material. The present study indicates a need for nondestructive surface examination of pericardial sheets for the elimination of areas of surface voids resulting from gross fiber disorientation. Also, there seems to be a need for incorporation of an in situ fiber renewal mechanism in bioprosthetic leaflets to emulate the natural valve more closely. Apparently natural leaflets have built-in fiber renewal mechanism(s).     

Patient-controlled epidural analgesia: demand dosing

A double-blind, placebo-controlled study was designed to compare the efficacy of demand-dose patient-controlled epidural analgesia (PCEA) with continuous epidural infusion (CEI) for treatment of pain during labor and delivery. Forty patients were randomized to receive 0.125% bupivacaine with fentanyl (2 micrograms/mL) through CEI at 12 mL/h or through demand-dose PCEA. Patients using PCEA could demand 3 mL every 10 min without restriction. Analgesia in both groups was comparable. However, there was a significant reduction in total bupivacaine consumption (in milligrams) associated with the use of PCEA (mean +/- SEM: CEI = 76.1 +/- 8.5 mg; PCEA = 42.2 +/- 5.9 mg; 45% reduction). The hourly bupivacaine consumption during the first (CEI = 15.8 +/- 0.6 mg/h; PCEA = 8.8 +/- 1.1 mg/h) and second (CEI = 17.2 +/- 1.2 mg/h; PCEA = 6.8 +/- 1.2 mg/h) stages of labor was also reduced. Overall, this represented a 47% "sparing" of bupivacaine use per hour with PCEA. Similar reductions occurred in the use of fentanyl. The reductions in analgesic requirement, however, were not associated with a reduction in the degree of motor blockade or in the cephalad extent of sensory blockade. A significant dose-sparing effect was associated with the use of demand-dose PCEA as compared with standard CEI for analgesia during labor and delivery.     

A preferential inhibition of impulses in C-fibers of the rabbit vagus nerve by veratridine, an activator of sodium channels.

In seeking a means to reverse local anesthetic block of peripheral nerve, we examined the actions of veratridine (VTD), an agent known to antagonize competitively the binding of local anesthetics to Na channels. The actions of VTD, a steroidal alkaloid "activator" of voltage-gated Na channels, were studied in the rabbit vagus nerve by two methods. In one, the effects of VTD on compound action potentials (APc) propagating through a "veratrinized" segment (11-mm) of nerve were measured by extracellular recording. Single volleys of impulses were unaffected by VTD, but trains of impulses, triggered by repetitive stimulation, were selectively diminished. This "use-dependent" reduction was greatest for the C-fiber component of the APc, less for B-fibers, and inconsequential for A-fibers. Use-dependent inhibition was enhanced by higher stimulation frequency and by increased VTD concentration, and reversed rapidly when stimulation ceased. If the nerve sheath remained intact, the rate of VTD action was far less than in desheathed nerves, but the effects were the same. In the other experimental system, membrane potentials were measured in the veratrinized region of the nerve by a sucrose-gap method. Repetitive stimulation, particularly of C-fibers, produced a cumulative VTD-induced depolarization (VID) that was sustained over several seconds and during which the C-fiber APc was selectively reduced. We propose that this local, use-dependent VID provides the means to inhibit impulses propagating through the veratrinized region. The preferential effect of VTD on C-fibers suggests its possibilities as a relatively selective agent for block of impulse trains in nociceptive afferents.     

The effect of leptin on luteinizing hormone release is exerted in the zona incerta and mediated by melanin-concentrating hormone

The adipose hormone, leptin, not only restrains appetite, but also influences energy expenditure. One such influence is to promote sexual maturation and fertility. The neuromodulatory circuits that mediate this effect are not well known but the present study suggests that one mediator could be melanin-concentrating hormone (MCH). We show that the long-form receptor (Ob-Rb) is expressed in the zona incerta of the rat and that administration of leptin (both 0.5 microg and 1.0 microg/side) into this area of ovariectomized, oestrogen-primed rats stimulated the release of luteinizing hormone (LH) within 1 h, the effect enduring for a further 1 h. Injections of leptin into the arcuate nucleus induced a smaller, transient rise in LH while injections into the paraventricular and ventromedial nuclei were without effect. MCH neurones are present in the zona incerta and administration of this hormone into the medial preoptic area (mPOA) stimulates LH release, therefore we investigated the possibility that MCH might mediate this effect of leptin. An injection of MCH antiserum into mPOA prevented the rise in LH normally induced by leptin injected into the zona incerta. In addition, melanocortin receptor antagonists ([D-Arg8]ACTH(4-10) and [Ala6]ACTH(4-10)), previously shown to inhibit the stimulatory effect of MCH on LH release, also inhibited the effect of leptin. We propose that one route by which leptin may promote reproductive activity is by enhancing MCH release from fibres within the mPOA. Speculative mechanisms for the action of MCH include the following possibilities: MCH may be acting on the specific MCH receptor which in turn interacts with a melanocortin or melanocortin-like receptor; MCH may bind directly to one of the melanocortin receptors; or melanocortin antagonists may interact with the MCH receptor.     

Dorsal subcoeruleus nucleus (SubCD) involvement in context-associated fear memory consolidation

The neurobiological mechanisms of emotional memory processing can be investigated using classical fear conditioning as a model system, and evidence from multiple lines of research suggests that sleep influences consolidation of emotional memory. In rodents, some of this evidence comes from a common finding that sleep deprivation from 0 to 6 h after fear conditioning training impairs processing of conditioned fear memory. Here, we show that during a 6-h session of sleep–wake (S–W) recording, immediately after a session of context-associated fear conditioning training, rats spent more time in wakefulness (W) and less time in slow-wave sleep (SWS) and rapid eye movement (REM) sleep. This context-associated fear conditioning training-induced reduction in SWS lasts for 2 h, and the REM sleep reduction lasts throughout the entire 6-h post-training S–W recording period. Interestingly, these reductions in SWS and REM sleep during this 6-h period did not impair memory consolidation for context-associated fear conditioning. The results of this study show, for the first time, that lesions within the dorsal part of the subcoeruleus nucleus (SubCD), which were unintentionally caused by the implantation of bipolar recording electrodes, impair consolidation of context-associated fear conditioning memory. Together, the results of these experiments suggest that emotional memory processing associated with fear conditioning can be completed successfully within less than a normal amount of sleep, but it requires a structurally and functionally intact SubCD, an area in the brain stem where phasic pontine wave (P-wave) generating cells are located.