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Biomedical subjects

F Henderson

Publications and source records attributed to F Henderson.

At least 19 recordsLinked to original sources
PubMed2000

2D CSI proton MR spectroscopy of human spinal vertebra: feasibility studies.

This report focuses on proton magnetic resonance spectroscopy (1H MRS) of spine vertebra acquired with two-dimensional chemical shift imaging (2D CSI), utilizing the stimulated echo acquisition mode (STEAM) sequence. Both validity and reproducibility studies were performed. To validate the 2D CSI method, its spectra were compared with those obtained with the single-voxel (SV) method. Five normal volunteers were scanned. The reproducibility of 2D CSI was examined by performing spectroscopy on two different occasions, on three normal volunteers. Data show that the STEAM 2D CSI technique results in MRI spectra comparable to those obtained with the STEAM SV method. 2D CSI offers significant time savings and convenient multi-voxel spectral analysis at a substantially higher signal-to-noise ratio. The 2D CSI method was then applied to a patient with a small vertebral hemangioma. The results demonstrated that the voxels containing the hemangioma exhibit different spectra than the neighboring voxels of the same vertebra. Additionally, a case of vertebral osteoporosis was investigated. Results showed a significant increase in the lipid-to-water ratio (LWR). It is suggested that 2D CSI may be powerful in identifying physiological as well as pathological changes of the bone marrow. Furthermore, covering a more extensive area of the vertebral body will maximize the chances of depicting a small focus of pathologic tissue. A more detailed bone marrow pattern was noticed in on one subject whose spectra show more lipid peaks.

Adult↗
PubMed2000

Contrasting effects of CCR5 and CCR2 deficiency in the pulmonary inflammatory response to influenza A virus.

The immune response to influenza A virus is characterized by an influx of both macrophages and T lymphocytes into the lungs of the infected host, accompanied by induced expression of a number of CC chemokines. CC chemokine receptors CCR5 and CCR2 are both expressed on activated macrophages and T cells. We examined how the absence of these chemokine receptors would affect pulmonary chemokine expression and induced leukocyte recruitment by infecting CCR5-deficient mice and CCR2-deficient mice with a mouse-adapted strain of influenza A virus. CCR5(-/-) mice displayed increased mortality rates associated with acute, severe pneumonitis, whereas CCR2(-/-) mice were protected from the early pathological manifestations of influenza because of defective macrophage recruitment. This delay in macrophage accumulation in CCR2(-/-) mice caused a subsequent delay in T cell migration, which correlated with high pulmonary viral titers at early time points. Infected CCR5(-/-) mice and CCR2(-/-) mice both exhibited increased expression of the gene for MCP-1, the major ligand for CCR2(-/-) and a key regulator of induced macrophage migration. These studies illustrate the very different roles that CCR5 and CCR2 play in the macrophage response to influenza infection and demonstrate how defects in macrophage recruitment affect the normal development of the cell-mediated immune response.

Animals↗
PubMed2000

Normal lumbar vertebrae: anatomic, age, and sex variance in subjects at proton MR spectroscopy--initial experience.

Fifty-seven subjects underwent proton magnetic resonance (MR) spectroscopy of the second lumbar vertebra to evaluate single-voxel and multivoxel techniques. Measurements included lipid-to-water ratios, lipid fractions, and line width. These data provide information about vertebral fat content. There was an age-dependent linear increase in fat content and sex dependence. A higher fat concentration was found in men. The observed spectra provide a basis for future study to determine clinical utility of vertebral proton MR spectroscopy.

Adolescent↗
PubMed1999

Controversies in anaesthesia--designer drugs.

In the past, the discovery of new drugs often occurred by chance. Over recent years, an increasing knowledge of the mode of drug action and receptor sites has improved our ability to design new drugs. While the mode of action of volatile and intravenous anaesthetic agents remains unclear, neuromuscular blocking agents and opioids have undergone considerable development and design. Drugs are being tailored to produce fewer side effects and to improve desirable properties. As a result, the introduction of new drugs has helped to improve techniques in anaesthesia. The development of remifentanil is an example of this which is discussed. The application of modern technology with target controlled infusions (TCI) for the administration of remifentanil represents further advancement in techniques which may become available to anaesthetists in the future.

Anesthesia↗
PubMed1994

Respiratory abnormalities due to craniovertebral junction compression in rheumatoid disease.

OBJECTIVE: To assess the extent and severity of respiratory insufficiency associated with severe rheumatoid atlantoaxial dislocation and its relation to compression of the neuraxis. METHODS: Twelve patients with severe atlantoaxial dislocation due to rheumatoid disease were studied. Detailed clinical, CT myelography and respiratory assessment including nocturnal oximetry, were performed on all patients. RESULTS: All patients were severely disabled by their underlying disease but none had symptoms of hypoventilation. All the patients with C1 compression had myelopathic features. Those with medullary deformation (moulding and/or stretch) had abnormal noctural oximetry whilst no significant desaturations were seen in the remaining patients. Post-operative studies showed resolution of noctural desaturations. CONCLUSION: This study suggests that clinically unsuspected respiratory insufficiency may be common in patients with severe medullary compression associated with rheumatoid atlantoaxial dislocation. It emphasises the importance of careful respiratory monitoring including nocturnal oxygen saturation in patients with major atlantoxial dislocation due to rheumatoid disease.

Aged↗
PubMed1992

Serum masks the inhibition of thrombin-induced prostacyclin release produced by anticardiolipin antibodies.

The effect on thrombin-induced release of prostacyclin from human umbilical vein endothelial cells of preincubation with both serum and serum derived from platelet-poor plasma (PDS) from patients with systemic lupus erythematosus (SLE), systemic sclerosis, the antiphospholipid syndrome (APS) and normal controls was examined. Although no significant differences in thrombin-induced prostacyclin release were found in any of the patient groups, further analysis revealed that PDS from patients with SLE and APS that contained IgG anticardiolipin antibodies produced significant inhibition of prostacyclin release when compared with controls (P = 0.02). The effect was maximal with samples that contained both IgG and IgM anticardiolipin antibodies (P less than 0.01) and which had a significantly higher titre of IgG antibodies than samples which contained solely IgG antibodies (P less than 0.05). The absence of any corresponding inhibition of prostacyclin release by serum samples that contained anticardiolipin antibodies, possibly due to the release of masking stimulatory factors by platelets during coagulation, provides an explanation for the conflicting nature of previous reports.

Adult↗
PubMed1990

End-plate ion channel block produced by lincosamide antibiotics and their chemical analogs.

Five lincosamide compounds were studied for their effects on end-plate currents (epcs), miniature end-plate currents and acetylcholine-induced current fluctuations in the garter snake costocutaneous nerve-muscle preparation. At high concentrations, lincomycin and clindamycin reduced epc amplitude, but analysis of driving functions showed that only with clindamycin was this due solely to changes in epc quantal content. The effect of lincomycin on epc amplitude was exaggerated by rapid channel block during the rising phase of the epc. Clindamycin produced currents with a single exponential decay and single Lorentzian noise spectra. All the other compounds produced currents which decayed as the sum of two exponential components. For lincomycin and epilincomycin, noise spectra consisted of two Lorentzian components. For epiclindamycin and deoxylincomycin, although epcs and miniature end-plate currents decayed with two components, it was not possible to separate two components in the noise spectra. A kinetic analysis of ion channel blocking actions showed only small differences between the two pairs of stereoisomers studied. End-plate ion channel blocking and unblocking rate constants did not vary greatly among the compounds but the end-plate ion channel unblocking rate constant values for the two lincomycin stereoisomers were larger than those for the two clindamycin stereoisomers. Deoxylincomycin exhibited properties similar to those of the clindamycins. It was concluded that lipid solubility, not stereochemical conformation, plays the greater role in determining the ion channel blocking properties within the series, particularly that of the rate of dissociation of the compound from end-plate ion channels.

Animals↗
PubMed1987

Rationalization and computerization of the drug supply to an animal unit.

Drug stocks in an animal unit were rationalized by discarding out-of-date or unwanted items and drawing up an approved stock list. A computerized system of stock control which enables a regular and accurate inventory of pharmaceuticals to be made was then established. In addition, the paperwork required for reordering drugs is produced automatically. Pharmaceuticals to a total value of 1650 pounds were discarded during the rationalization phase. The value of drugs stocked in the animal unit then stabilized at about one-third of previous levels. In the first 6 months of operation of the new system drug expenditure fell by about 40% in comparison with the same period 1 year previously. The drug stock control system has proved economical to operate and accurate, and can be run by persons without computer expertise. Valuable savings in both cost and labour have resulted. Effective management of drug expenditure by the animal unit is now possible.

Animals↗
PubMed1986

The effects of chloramphenicol isomers on the motor end-plate nicotinic receptor-ion channel complex.

Four enantiomers of chloramphenicol have been tested for their effects on end-plate current and miniature end-plate current decay and amplitude characteristics in the voltage-clamped costocutaneous nerve-muscle preparation of the garter snake. All four enantiomers exhibited effects on end-plate current and miniature end-plate current decay at similar concentrations (0.2-1.0 mM), indicating that the measured effect was not related to the antibacterial action of the compounds in which D-threo chloramphenicol is known to be at least 50 times more powerful than the L-threo and D- and L-erythro isomers. The compounds slightly increased end-plate current but not miniature end-plate current amplitude, indicating that they produce an increase in end-plate current quantal content. This effect was verified by an analysis of end-plate current driving functions (see Appendix) for one of the chloramphenicol isomers. In addition to this presynaptic action, all four compounds converted end-plate current and miniature end-plate current decays from single to double exponential functions. This effect was both concentration and voltage dependent. For all four compounds, hyperpolarization resulted in a progressive decrease in tau f and an increase in tau s. The relative amplitudes of the fast and slow decay components were independent of membrane potential. The results are interpreted in terms of the drugs blocking the open form of the acetylcholine-activated receptor-ion channel complex. However, in addition to affecting decay characteristics, all four compounds increased the charge passed during both end-plate and miniature end-plate currents. This effect was concentration but not voltage dependent and is inconsistent with the predictions of the sequential model for open ion channel blockade. By using an extension of Ruff's analysis of the sequential model of open end-plate ion channel blockade, we have been able to show that the action of the chloramphenicols on end-plate current amplitude and time course can be explained by the combination of two distinct mechanisms. First is an open channel block conforming to the sequential model and with calculated channel blocking affinity constants ranging from 0.3-1.0 mM. The channel blocking actions of all four isomers were shown to be independent of membrane voltage. Second is an action to slow channel closing, resulting in prolonged open time and hence increased charge passed during the end-plate current. This effect was strongly concentration dependent, but not voltage dependent.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

The effects of the antibiotic, primycin, on spontaneous transmitter release at the neuromuscular junction.

The effects of primycin, a potent ionophore in biological membranes, have been studied at the neuromuscular junction of the garter snake. Primycin in concentrations greater than 2 X 10(-7)M produced a time- and concentration-dependent depolarization of twitch muscle fibres. Primycin (10(-7)-5 X 10(-7)M) produced an increased rate of quantal release of acetylcholine, which was not maintained, and a slight reduction in quantal size. Time to onset and to peak effect of primycin were concentration-dependent whereas maximum frequency was not. Absence of extracellular Ca2+ produced a significant delay in the time to onset and to peak effect of primycin, but did not affect the peak miniature endplate potential (m.e.p.p.) frequency. Following 60 min exposure to primycin (5 X 10(-7)M), introduction of a high concentration of potassium (20 mM) produced no further increase in spontaneous release. In cut muscle preparations, exposure to primycin (10(-7)-5 X 10(-7)M) reduced peak endplate current (e.p.c.) amplitude until nerve stimulation resulted in failures or the release of one or two quanta. E.p.c. amplitude was not restored with prolonged washing. The effects of primycin on the nerve terminal are considered to be consistent with its ability to increase the permeability of membranes to calcium ions resulting in an influx of extracellular calcium, an efflux of mitochondrial calcium and eventual depletion of synaptic vesicles.

Animals↗
PubMed1983

Comparative effects of clindamycin and lincomycin on end-plate currents and quantal content at the neuromuscular junction.

The pre- and postjunctional effects of the lincosamide antibiotics, clindamycin and lincomycin, were studied in voltage-clamped transected twitch fibers of costocutaneous muscles of garter snakes (species Thamnophis). Miniature end-plate currents and end-plate currents (EPCs) were recorded over a wide voltage range for each antibiotic. The amplitude and kinetics of these currents were studied and estimates of the quantal content of evoked transmitter release determined. High concentrations of clindamycin (2 X 10(-4) M) and lincomycin (2 X 10(-3) M) produced significant depression of EPC amplitude and a nonlinearity in the EPC-voltage relationships. The time constant of EPC decay was accelerated in clindamycin and the relationship between the time constant of EPC decay and membrane potential remained a single exponential function with a concentration-dependent loss of the voltage dependence. In contrast to clindamycin, lincomycin produced biphasic EPCs which consisted of two components, one faster and one slower than the control decay rate. The relative amplitude and decay rate of each component was both concentration and voltage dependent. Either increasing the concentration of lincomycin or membrane hyperpolarization decreased the amplitude ratio, iota slow/iota fast, and increased the ratio of the respective time constants, tau slow/tau fast. Clindamycin affected EPC decay amplitude and quantal content in the same concentration range, whereas lincomycin affected EPC decay at concentrations 20 times less than those required to reduce EPC amplitude and quantal content. These results suggest that the neuromuscular blocking effects of clindamycin involve both pre-and postjunctional sites, whereas the effects of lincomycin are primarily on the postjunctional receptor-channel complex.

Animals↗
PubMed1977

Identification of Rickettsia rickettsii in a guinea pig model by immunofluorescent and electron microscopic techniques.

Moribund guinea pigs infected with Richettsia rickettsii were examined by necropsy, histology, immunofluorescence, electron microscopy, and serology. Untreated animals died at 9 and 10 days after inoculation. Animals given saline subcutaneously survived from 1 to 4 days longer. Prolonged survival was accompanied by more severe lesions: scrotal necrosis; infarction of ears; and swollen, hemorrhagic footpads, epididymis, and cremaster muscle. Histopathologic examination demonstrated that acute, necrotizing vasculitis, perivascular hemorrhage, and focal necrosis were more extensive. Direct immunofluorescence indicated many more rickettsiae in endothelium and vascular wall of saline recipients. Ultrastructurally, typical rickettsiae were present focally in the cytoplasm of endothelial and vascular smooth muscle cells. Cytopathology in infected and adjacent cells included swelling, mitochondrial enlargement with decrease in matrix density and loss of cristae, and increased pinocytosis. In addition, treated animals had more cytonecrosis, thrombosis, extravascular fibrin deposition, prominent inflammatory cells with polymorphonuclear phagocytosis of rickettsiae, and antibody production.

Animals↗