Hickman catheter and implantable port devices for the delivery of chemotherapy: a phase II randomised controlled trial and economic evaluation.

BACKGROUND: In the United Kingdom, totally implantable venous access systems (TIVAS) are not routinely used. Compared with Hickman catheters, these devices are more expensive and complex to insert. However, it is unclear whether the higher costs may be offset by perceived greater health benefits. This pilot trial aimed to generate relevant data to inform the design of a larger definitive randomised controlled trial. METHODS: This was a phase II prospective, randomised, open trial from two UK oncology centres. The primary end point was overall complication rate. Secondary end points included individual complication rates, time to first complication and quality of life. Analysis was by intention to treat. An economic evaluation was also carried out. RESULTS: A total of 100 patients were randomised in a 3 : 1 ratio to receive a Hickman or a TIVAS. Overall, 54% of patients in the Hickman arm suffered one or more complications compared with 38% in the TIVAS arm (one-sided P=0.068). In the Hickman arm, 28% of the devices were removed prematurely due to a complication compared with 4% in the TIVAS arm. Quality of life based on the device-specific questionnaire was greater in the TIVAS arm for 13 of the 16 questions. The economic evaluation showed that Hickman arm was associated with greater mean cost per patient £1803 (95% CI 462, 3215), but similar quality-adjusted life years -0.01 (95% CI -0.15, 0.15) than the TIVAS arm. However, there is much uncertainty associated with the results. CONCLUSIONS: Compared with Hickman catheters, TIVAS may be the cost-effective option. A larger multicentre trial is needed to confirm these preliminary findings.

Junctional physiology and motor nerve distribution in the fast adductor muscle of the scallop.

Electrical recordings from single muscle cells in the fast portion of the scallop adductor have revealed a multiterminal distribution of motor nerves. All motor junctions appear to be of the fast designation, and several nerve fibers supply each muscle cell. The muscle fibers, by virtue of common innervation, are grouped into functional motor units. The pattern of innervation in scallops thus shares functional similarities with the motor distribution to skeletal muscle fibers of both vertebrates and arthopods.

Analysis of compound postsynaptic potentials in the central nervous system of the surf clam.

Compound postsynaptic potentials, comprising graded excitatory-inhibitory sequences, are the characteristic mode of response to afferent input exhibited by a population of cells in the visceroparietal ganglion of Spisula. Experimentally induced interaction between the phases of the response indicates that the observed sequential invasion represents differences in individual component latencies, rather than the physiological resultant of two separate processes having simultaneous onset but different rates of decay. Excitation is depressed by changes in membrane conductance throughout the duration of the inhibitory phase; moreover, since similar pathways from the periphery initiate both phases, excitatory events are limited to a duration roughly equal in length to the latency for the inhibition. Within this interval repetitive volleys can evoke summation of excitatory events. The inhibitory mechanism is temporally stable, however, and dominates the membrane during repetitive trains of volleys at 1 to 100 per sec. Artificially generated increases in the membrane potential decrease the IPSP while increasing the amplitude of the EPSP. Thus, both phases of the compound response appear to result from events occurring at chemically transmitting synaptic loci. Evidence is presented that these events are driven via collaterals of the same afferent fibers. The behavioral role of these response sequences is uncertain. Analogies, in terms of some observed reflex activity in these clams, appear to exist but presently lack experimental verification.

Nontopographic projection of olfactory sensory neurons in the crayfish brain.

We have used tritiated leucine to trace the input projection pattern of olfactory sensory neurons in crayfishes. The olfactory neurons are associated with cuticular sensilla on the external antennular filaments. Each sensillum, or aesthetasc, harbors the distal dendritic segments of about 175 bipolar sensory neurons, the cell bodies for which are grouped in a subcuticular ensemble or ganglion. About 150-175 individual ganglia may be found on each antennule in an adult crayfish. When an aesthetasc is exposed to tritated leucine, the tracer is taken up by the associated olfactory sensory neurons and is transported along the axons to their central terminations within the glomeruli of the ipsilateral olfactory lobe. We tested the possibility that the sensory neurons from specific aesthetascs project to specific glomeruli. By restricting access of the leucine to small groups of aesthetascs, we exposed less than 2% of the olfactory sensory neurons to the tracer. Nonetheless, all glomeruli were labeled following such treatment. We conclude that the sensory neurons are generally distributed to the olfactory glomeruli. If each neuron terminates in a single glomerulus, these data support a divergent pattern of sensory projection from individual ganglia to all regions of the olfactory lobe.

Anatomy and fine structure of neurons in the deutocerebral projection pathway of the crayfish olfactory system.

Golgi impregnation and neurobiotin injection were used to examine details of the neural pathways in the olfactory system of the freshwater crayfish, Procambarus clarkii. Deutocerebral projection neurons (globuli cells) were directly injected with neurobiotin. These neurons have dendritic arborizations in the ipsilateral olfactory and accessory lobes, and they project axons to the lateral protocerebrum, where they terminate in microglomeruli of the hemi-ellipsoid body. The axons of the deutocerebral projection neurons are readily impregnated by Golgi procedures, and they terminate as an expanded membranous knot about 5 microns in diameter. Electron microscopy on Golgi-stained terminals has revealed that each knot makes several hundred synapses with small spine-like or shaft-like processes of postsynaptic neurons. Injection of neurobiotin into local interneurons of the hemi-ellipsoid body and subsequent examination of stained preparations with the electron microscope reveals that these cells are a major postsynaptic target of the deutocerebral projection neurons. Furthermore, the local interneurons make extensive efferent synaptic connections with unidentified neurons in the terminal medulla.

Distribution of radioactive leucine following uptake by olfactory sensory neurons in normal and heteromorphic crayfish antennules.

Surgical excision of one of the compound eyes from juvenile crayfish leads to the regeneration of a heteromorphic antennule in 30% of the cases. Most of the heteromorphic antennules generated this way are bifurcate appendages possessing morphologically distinct medial and lateral branches. These structures are identical to the internal and external flagella of the normal antennules, and the homolog of the external flagellum bears aesthetascs supplied by olfactory sensory neurons. Autoradiographic analysis of the brain following exposure of heteromorphic antennules to tritiated leucine indicates that the supernumerary sensory axons transport the labeled amino acid into their central terminals at appropriate target locations within the ipsilateral olfactory lobe. The data suggest that olfactory input from heteromorphic antennules is incorporated into the organized central projection of olfactory afferents from the normal antennule.

Cellular organization and growth-related plasticity of the crayfish olfactory midbrain.

Little knowledge is available concerning the detailed anatomy of the crusctacean central olfactory pathway. We are using radiolabeling, Golgi and biocytin/neurobiotin tracer methodologies, at the correlated light and electron microscopical levels, to study the olfactory midbrain of the freshwater crayfish. We have found that primary afferent fibers from the antennular olfactory receptor cells branch extensively throughout the length of the glomerular columns within the olfactory lobes in the midbrain. Globuli cells of the lateral cell clusters ramify as dendritic arborizations within both the olfactory and accessory lobes; their axons project out the olfactory-globular tracts to the lateral protocerebrum, often branching to both sides. Developmental plasticity involving the connections made by afferent fibers within the olfactory lobes may permit detailed examination of organizational changes within the midbrain as the animal grows and adds new afferent input from the periphery.

Nitric oxide as a putative messenger molecule in the crayfish olfactory midbrain.

NADPH-d histochemistry was used to investigate presumptive nitric oxide synthase (NOS)-containing neurons in the crayfish olfactory midbrain. Three anatomically different types of local olfactory interneurons exhibiting NADPH-d activity were observed: two pairs of large interneurons as well as positively stained globuli cells. Branches derived from the large interneurons were confined to the ipsilateral olfactory lobe and accessory lobe, but only a few branches innervated the olfactory lobe glomeruli. Local field potential recordings on the olfactory lobe showed that administration of SNP or SIN-1 (10-4 M) into the brain had reversible inhibitory effects on electrically-evoked responses of unidentified neuronal cell populations.

Modification of motor neuron size and position in the central nervous system of adult snapping shrimps.

Cell bodies of claw closer motor neurons in snapping shrimp are dimorphic. Snapper claw motor neurons are larger than corresponding pincer claw motor neurons, but the relative sizes of these cells are reversed during claw transformation. An additional neuronal modification occurs early within this period, in that the pincer claw dorsal inhibitor cell body migrates within the nervous system, from a dorsal to a ventral position. These findings are evidence of rapid, reversible changes in the nervous system following the trigger for the transformation process.

The organization of the central nervous connectives in Anodonta cygnea (Linnaeus) (Mollusca : Eulamellibranchia).

The cerebro-visceral connective of Anodonta cygnea comprises a non-cellular neural lamella, a few randomly distributed glial elements, and axons, together with an extensive extracellular system. The axons are relatively small, the majority being less than 2.0 micro in diameter. The neural lamella is underlaid by a thin layer of peripheral glial processes. The membranes of the proximate glial processes do not reveal any junctional complexes at this level. In addition to glycogen and fat deposits, the glial cytoplasm contains abundant 'glial granules' which in histochemical tests react like mucoproteins. The extracellular space appears to be freely accessible, for apart from the neural lamella no other visible structures are interposed between it and the fluid surrounding the connective. These structural findings are discussed in relation to the available evidence concerning the ability of axons to function in preparations bathed in low-sodium media.

Extrinsic tracheal compression--a newly described complication of acquired immune deficiency syndrome (AIDS).

An AIDS patient was seen in respiratory difficulty with a superior mediastinal mass. Examination revealed a candida fungoma. To the best of our knowledge, this is the only case of its nature. The differential diagnosis and management of this patient are presented in detail.

Convergence of multimodal sensory input onto higher-level neurons of the crayfish olfactory pathway.

Intracellular electrophysiological studies of lateral protocerebral interneurons (LPIs) in the crayfish Procambarus clarkii have revealed convergence of multimodal sensory information onto these higher-level cells of the crustacean central olfactory pathway. Antennular stimulation by odors or electrical shocks generates excitatory-inhibitory sequences in some LPIs as does electrical or hydrodynamic stimulation of the antennae. Photic stimulation of the ipsilateral compound eye generates excitatory responses in LPIs, usually in the form of trains of impulse bursts that are timed to the peaks of the spontaneous oscillatory activity that characterizes these neurons. Focal electrical stimulation of the olfactory lobe, the termination point of antennular afferent input, or the accessory lobe, where higher-level visual and tactile inputs converge, also generates brief excitation and a delayed, prolonged inhibition in LPIs. Both phases of this activity are thought to be transmitted to the lateral protocerebrum via deutocerebral projection neurons, which have extensive dendritic arborizations in the olfactory lobe and the accessory lobe. The excitatory pathway is thought to synapse directly with target LPIs, whereas the inhibitory pathway is probably indirect and mediated through GABAergic interneurons within the lateral protocerebrum. There is evidence that both presynaptic and postsynaptic inhibition suppress activity in LPIs. Preliminary observations suggest that a small cluster of neurons adjacent to the hemi-ellipsoid body are inhibitory to LPI activity. Multimodal inhibitory and excitatory modulation of LPI activity may play a part in the contextual identification of odors in the crayfish olfactory system.

Structure and electrical properties of eye muscles in cave- and surface-dwelling crayfishes.

The morphologies and passive electrical parameters of fibres in two eye muscles of a surface- and a cave-dwelling crayfish were compared. In the cave-dwelling form the muscles contained fewer fibres, of less diameter, and hence had a smaller cross-sectional area. Current-voltage relationships were similar in both species. Input resistance was higher in the cave-dweller, but the difference was not as great as would be expected on the basis of geometry alone. Accordingly, the specific membrane resistance of muscle fibres in the cave-dweller is 50-60% smaller than that in the surface-dweller. This may account partially for the observation that identified excitatory junctional potentials in muscles of cave- and surface dwellers have similar amplitudes. We conclude that a functional oculomotor system is maintained in cave-dwelling crayfish, and that this system confers some positive selective advantage.

The rare presentation to the cosmetic and plastic surgeon of a patient with myxedema.

Myxedema results from hypofunction of the thyroid gland. Symptoms include dry skin, loss of and dryness of hair, mental apathy, drowsiness, and sensitivity to cold. Ocular complications associated with myxedema may be the symptoms that first prompt patients to seek a physician or cosmetic surgeon, however, though other symptoms may be present before eyelid myxedema occurs. The case reported here illustrates the value of a correct diagnosis and appropriate medical treatment, and demonstrates how surgical intervention to correct remaining eyelid problems can succeed when it is part of a comprehensive treatment plan.

Disruption of muscle reorganization by lesions of the peripheral nerve in transforming claws of snapping shrimps.

We have performed surgical transections on nerves in the transforming claws of snapping shrimps. In normal transformation muscle restructuring occurs, involving degeneration of some fibers and biochemical changes in others. Surgical section of the entire second limb nerve root or of its distal, dorsal branch--both of which contain the motor axons to the closer muscle--prevents muscle restructuring, even though transformation of external claw morphology proceeds. Furthermore, nerve lesions must be performed within a specific time period after transformation has been triggered in order for the effects to be observed. We suggest that transformation involves an early sensitization of the targeted muscle and that this process depends upon an intact nervous pathway within the second nerve root.