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Biomedical subjects

D Sawyer

Publications and source records attributed to D Sawyer.

At least 19 recordsLinked to original sources
PubMed2001

The pseudomonas hot-foot syndrome.

BACKGROUND: Between March and May 1998, there was an outbreak of a clinically distinct skin eruption on the soles of the feet of children who used a community wading pool. METHODS: We reviewed the medical records of 40 children in whom this syndrome developed between March and May 1998. We treated 17 children and advised the attending physicians on the care of the other 23. Follow-up data were obtained for up to one year. RESULTS: Exquisitely painful erythematous plantar nodules developed in 40 children (age, 2 to 15 years) within 40 hours after they had used a wading pool whose floor was coated with abrasive grit. Culture of the plantar pustules from one child yielded Pseudomonas aeruginosa with a pattern on pulsed-field gel electrophoresis that was identical to that of a strain of P. aeruginosa cultured from the pool water. A skin-biopsy specimen from this patient showed a perivascular and perieccrine neutrophilic infiltrate, and a specimen from another patient showed a dermal microabscess. Thirty-seven patients were treated symptomatically; three others were treated with cephalexin. All patients recovered within 14 days, but three children had recurrences of the painful plantar nodules within 24 hours after using the pool again. Folliculitis developed in one patient. CONCLUSIONS: The "pseudomonas hot-foot syndrome" is characterized by the acute onset in children of exquisitely tender plantar nodules and a benign, self-limited course. This community outbreak developed after exposure to pool water containing high concentrations of P. aeruginosa.

Adolescent↗
PubMed1998

Effects of volatile anaesthetics on a high conductance calcium dependent potassium channel in cultured hippocampal neurons.

(1) The effects of isoflurane and halothane (at nominal concentrations of 4%) were studied on a high conductance Ca2+-dependent K+ channel using inside-out patches from cultured rat hippocampal neurons. (2) With physiological-like concentrations of K+ across patches (140 mM internal and 5 mM external), unitary activity from a 4 pA channel (conductance near 100 pS) was evident in excised patches. (3) Isoflurane or halothane had no effects on unitary properties of K (Ca) including channel amplitudes and open and closed times. The channel open probability was also unchanged in the presence of the volatile agent. The results suggest that macroscopic high conductance K (Ca) currents in hippocampal neurons would be relatively insensitive to high concentrations of inhalational anaesthetics.

Anesthetics, Inhalation↗
PubMed1997

Notifying patients exposed to blood products associated with Creutzfeldt-Jakob disease: integrating science, legal duties and ethical mandates.

The issue of notifying people who have been exposed to blood products that have been associated with Creutzfeldt-Jakob disease (CJD) has arisen at a time when the Canadian blood system is under intense scrutiny. As a result, the Canadian Red Cross Society issued a recommendation to health care institutions that recipients of CJD-associated blood products be identified, notified and counselled. Although Canadian jurisprudence in the realm of informed consent may support a policy of individual notification, a review of the scientific evidence and the applicable ethical principles arguably favours a policy of a more general public notification. Indeed, situations such as this require a unique approach to the formation of legal and ethical duties, one that effectively integrates all relevant factors. As such, the authors argue that individual notification is currently not justified. Nevertheless, if a system of general notification is implemented (e.g., through a series of public health announcements), it should provide, for people who wish to know, the opportunity to find out whether they were given CJD-associated products.

Beneficence↗
PubMed1997

Early fetal development of lung vasculature.

Despite its relevance to a variety of congenital anomalies, the earliest stages of lung vascular development are poorly understood. In other organs, two processes have been identified: vasculogenesis, the development of blood lakes in mesenchyme, and angiogenesis, the branching of new vessels from preexisting ones. In the present study we established the events in the development of the lung's vasculature in Swiss-Weber mouse fetuses between 9 and 20 days gestation, using light microscopy (LM), transmission electron microscopy (TEM), barium-gelatin angiograms, and scanning electron microscopy (SEM) of Mercox (methyl methacrylate) vascular casts. Three features were identified: (1) central sprouting or angiogenesis for up to approximately seven generations (counting the artery to each lung as first generation); (2) the formation of peripheral lakes by vasculogenesis; and (3) the development of communications between the central and peripheral systems. At 9 days gestation, intercellular spaces were apparent in the lung mesenchyme; these were formed by discharge of vesicles from mesenchymal cells, which then regrouped to provide "endothelial" cells lining the spaces. The isolated lakes coalesced to form sinusoidal spaces of irregular profile. At 12 days gestation, the earliest time at which were able to make a cast, sprouting of arteries and veins from the central pulmonary vascular trunks was apparent. Between 13 and 14 days gestation the earliest connection between the peripheral and central spaces was identified. Such connections became more numerous and dense by term. Similar images seen on examination of human fetal lung sections by LM indicated that similar processes occur in the vascular development of the human lung.

Animals↗
PubMed1995

Cation and anion unitary ion channel currents in cultured bovine microglia.

The use of excised patches has led to the identification and characterization of two channels not previously reported in microglia. A calcium-dependent K+ channel K(Ca) was activated in inside-out patches obtained from cultured bovine microglia and had a unitary conductance of 240 pS with symmetrical 140 mM K+ across patches. Mean open times of K(Ca) were exponentially dependent on patch potential and were increased with patch depolarization. Channel open probability (Popen) was increased with patch depolarization with either 5 mM or 140 mM internal K+ and was attributable to potential dependent enhancement of both opening frequency and mean open time. Whole cell currents showed the presence of a slowly activating K+ conductance, blocked by external TEA (at 2 mM) and likely the macroscopic correlate of the unitary K(Ca); half-maximal activation of the current occurred at +25 mV. An anion channel (unitary conductance of 325 pS with symmetrical Cl- across patches) was activated in inside-out patches with depolarizing and hyperpolarizing potential steps from 0 mV. Channel activation was not dependent on internal Ca2+. The anion currents inactivated during maintained potential steps with the time constant for inactivation faster with increased patch depolarization. The properties of the K(Ca) and anion channels in microglia membrane may have relevance to cell function in response to neuronal damage in the CNS.

Animals↗
PubMed1994

Interactions of dextromethorphan with the N-methyl-D-aspartate receptor-channel complex: single channel recordings.

The actions of dextromethorphan (DXM) on the 50 pS conductance state of the N-methyl-D-aspartate (NMDA) receptor-operated channel were studied using outside-out patches obtained from cultured rat hippocampal pyramidal neurons. DXM (5-50 microM) had no effect on the amplitudes of unitary currents but caused concentration-dependent reductions in channel mean open times and the frequency of channel openings. Channel open probability was reduced in a concentration-dependent manner by DXM and was one-half of the control value at a DXM concentration of 6 microM, with the patch potential held at -60 mV. An IC50 value of 4 microM was obtained for the reduction by DXM of NMDA-evoked rises in [Ca2+]i in cultured rat hippocampal pyramidal neurons loaded with Fura-2. The results were consistent with drug block of the open NMDA channel with an onward (blocking) rate constant of 7.7 x 10(6) M-1.s-1 (at -60 mV). The estimated unblocking rate constant was about 10 s-1, a value considerably higher compared to the off-rate constant found for dizocilpine block of the NMDA channel.

Animals↗
PubMed1994

The actions of L-687,384, a sigma receptor ligand, on NMDA-induced currents in cultured rat hippocampal pyramidal neurons.

The actions of the sigma receptor ligand L-687,384 were studied on N-methyl-D-aspartate (NMDA)-induced currents recorded from outside-out patches obtained from cultured rat hippocampal pyramidal neurons and on NMDA-evoked rises in [Ca2+]i in the same preparation. L-687,384 did not change the magnitudes of unitary NMDA currents or frequency of channel-openings but diminished channel-open probability by decreasing mean open time. This action was consistent with a voltage-dependent open-channel block of the NMDA channel by L-687,384 with a blocking rate constant of 5.9 x 10(6) M-1 s-1 at -80 mV. L-687,384 also reduced NMDA-evoked rises in [Ca2+]i in Fura-2-loaded neurons with an apparent IC50 value of 49 +/- 8 microM. The results demonstrate that L-687,384 acts as an antagonist at the NMDA receptor-channel complex.

Animals↗
PubMed1993

Dependence of single channel properties of the N-methyl-D-aspartate ion channel on stereoisomer agonists.

The cell-attached patch-clamp configuration has been used to determine the single channel properties of the N-methyl-D-aspartate (NMDA) ion channel with activation of the NMDA receptor by stereoisomer agonists. All of the agonists studied, including the L and D forms of N-methyl-aspartate and the L and D forms of homocysteate, activated a 42-pS conductance channel in cultured hippocampal neurons. For all agonists, the mean open times of the channel were diminished with increased patch hyperpolarization and exhibited an exponential dependence on potential over the range -40 mV to -120 mV. The mean open times, for patch potentials close to resting potential, and the mean frequencies of channel openings, at all patch potentials, were significantly different between each member of the stereoisomer pairs. For both L-homocysteate and NMLA, a fourfold increase in the patch pipette concentration caused an approximate quadrupling in the frequency of unitary events, with no significant change in mean open time. The open channel probability was used as a measure of agonist potency, and, at a concentration of 30 microM, NMDA and L-homocysteate were significantly more potent (P open in excess of 1.5%) than the corresponding stereoisomer compounds NMLA and D-homocysteate (P open near 0.3%). The relative potencies of the stereoisomer pairs were in reasonable agreement with the potency ratios measured in binding studies.

Animals↗
PubMed1993

Effects of divalent cations on the activation of a calcium-dependent potassium channel in hippocampal neurons.

The activation of a calcium-dependent K+ channel K(Ca) in cultured hippocampal neurons has been studied after the addition, to the internal solution, of the divalent cations magnesium (Mg2+), strontium (Sr2+) or barium (Ba2+). With physiological K+ across inside-out patches and Ca2+ present at 0.2 mM in the bath solution, a 90-pS channel was activated with an open probability in excess of 75%. When the internal Ca2+ was reduced to levels near 5 microM, the channel-open probability was significantly diminished. However, if 0.2 mM concentrations of either Mg2+ or Sr2+ were added to the internal solution, the open probability was increased to a value close to original level. In the presence of internal Ca2+ at 0.1 microM, the K(Ca) channel was not active and was not activated with the addition of 0.2 mM Mg2+ or Sr2+ to the internal solution. Thus, Mg2+ or Sr2+ were not able to active K(Ca) in the absence of Ca2+; however, both of these divalent cations could potentiate the Ca(2+)-induced activation of K(Ca) if internal Ca2+ was near 5 microM. The results indicate that Mg2+ could have a role as an internal modulator of K(Ca) in the Ca(2+)-dependent regulation of excitability in nerve membrane. Replacement of Ca2+ with Ba2+, or addition of Ba2+ to Ca-containing solutions, caused significant decreases in the channel-open probability for K(Ca). The action of Ba2+ was primarily mediated by a decrease in the frequency of channel opening. At a concentration of 5 microM, Ba2+ diminished the channel-open probability by one-half.

Animals↗
PubMed1993

Economic and social consequences of malaria in new colonization projects in Brazil.

The success or failure of colonization in frontier areas of Brazil is an important question because of the country's declared commitment to undertake agrarian reform. However, demographic analyses of settler populations in new frontier areas suggests that these areas are not retaining agricultural settlers, but attracting transient wage-labourers in ranching, mining, construction and entrepreneurial activities such as placer mining or small businesses. One reason for this trend is the high prevalence of endemic diseases such as malaria within frontier areas. High malaria prevalence interferes with the scope and stability of permanent, agricultural settlement and this imposes economic and social costs which extend far beyond immediate need for control and treatment of the disease.

Adolescent↗
PubMed1992

Tedisamil blocks a calcium-dependent potassium channel in cultured motoneurons.

A calcium-dependent potassium channel K(Ca) has been isolated in mouse motoneurons. With physiological concentrations of potassium across inside-out patches, a 100 pS K(Ca) channel was activated when the bath solution of Ca2+ was in excess of 1 microM. Introduction of the drug tedisamil, a blocker of repolarizing potassium channels in cardiac cells, at concentrations in the range 0.2-10 microM, caused a dose-dependent decrease in the mean open times for K(Ca). The drug action was consistent with open channel block of K(Ca) with an onward (blocking) rate constant of 6 x 10(7) M-1 s-1. Tedisamil, at concentrations of 1 microM and 5 microM, also blocked the K(Ca) channel when applied to outside-out patches with a similar potency as found with internal application. A large conductance K(Ca) channel in hippocampal neurons is also blocked by a number of putative Class III antiarrhythmic drugs, including tedisamil; thus, these agents may have utility in the characterization of the properties of K(Ca) channels in various cells.

Animals↗
PubMed1992

Temporary iridium-192 implant in the management of carcinoma of the prostate.

The controversy about the treatment of carcinoma of the prostate has increased in the last decade, with most urologists favoring radical prostatectomy rather than primary irradiation. Several reports of persistent tumors in 50% to 90% of patients after external irradiation and permanent iodine-125 implantation of the prostate have been disturbing. From July 1977 to December 1985, 200 patients with adenocarcinoma of the prostate were treated by combining bilateral pelvic lymphadenectomy and temporary interstitial iridium-192 implantation of the prostate, followed by external irradiation. Seventy-four (36%) patients underwent biopsies of the prostate 4 months to 2 years after completion of the irradiation. Only 12 (16%) patients had persistent tumors. Complications were minimized subsequently by dose modifications.

Adenocarcinoma↗
PubMed1991

The actions of intermediate and long-chain n-alkanols on unitary NMDA currents in hippocampal neurons.

The actions of the n-alkanols butanol, pentanol, and octanol on unitary currents passing through N-methyl-D-aspartate (NMDA) ion channels have been studied in cultured CA1 hippocampal neurons. The cell-attached patch clamp method, with L-homocysteic acid included in the patch pipette, was used to record single channel NMDA currents at the cell resting potential or for hyperpolarizing patch potentials. With the n-alkanols added to the bath solution, the mean open times for the NMDA channel were diminished and the channel conductance was unchanged. A decrease in mean open time to about 70% of control value was found with butanol (3 mM), pentanol (1 mM), and octanol (0.02 mM). In addition the n-alkanols had small effects to decrease the frequency of channel openings and to increase the amplitude of the unitary currents. The effects of the alcohols on intracellular calcium levels, during NMDA applications, were also measured using the fluorescent dye FURA II.

Alcohols↗
PubMed1990

Ca2(+)-mobilising properties of synthetic fluoro-analogues of myo-inositol 1,4,5-trisphosphate and their interaction with myo-inositol 1,4,5-trisphosphate 3-kinase and 5-phosphatase.

The ability of two fluoro-analogues of D-myo-inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) to mobilize intracellular Ca2+ stores in SH-SY5Y neuroblastoma cells has been investigated. DL-2-deoxy-2-fluoro-scyllo-Ins(1,4,5)P3 (2F-Ins(1,4,5)P3) and DL-2,2-difluoro-2-deoxy-myo-Ins(1,4,5)P3 (2,2-F2-Ins(1,4,5)P3) were full agonists (EC50s 0.77 and 0.41 microM respectively) and slightly less potent than D-Ins(1,4,5)P3 (EC50 0.13 microM), indicating that the axial 2-hydroxyl group of Ins(1,4,5)P3 is relatively unimportant in receptor binding and stimulation of Ca2+ release. Both analogues mobilized Ca2+ with broadly similar kinetics and were substrates for Ins(1,4,5)P3 3-kinase but, qualitatively, were slightly poorer than Ins(1,4,5)P3. 2F-Ins(1,4,5)P3 was a weak substrate for Ins(1,4,5)P3 5-phosphatase but 2,2-F2-Ins(1,4,5)P3 was apparently not hydrolysed by this enzyme, although it inhibited its activity potently (Ki = 26 microM).

Animals↗
PubMed1990

Calcium binds cooperatively to the regulatory sites of the cardiac thin filament.

To investigate the relationship between thin filament Ca2+ binding and activation of the MgATPase rate of myosin subfragment 1, native cardiac thin filaments were isolated and characterized. Direct measurements of 45Ca binding to the thin filament were consistent with non-cooperative binding to two high affinity sites (Ka 7.3 +/- 0.8 x 10(6) M-1) and either cooperative or non-cooperative binding to one low affinity site (Ka 4 +/- 2 x 10(5) M-1) per troponin at 25 degrees C, 30 mM ionic strength, pH 7.06. Addition of a low concentration of myosin subfragment 1 to the native thin filaments produced a Ca2+-regulated MgATPase activity with Kapp (2.5 +/- 1.3 x 10(5) M-1), matching the low affinity Ca2+ site. The MgATPase rate was cooperatively activated by Ca2+ (Hill coefficient 1.8). To determine whether Ca2+ binding to the low affinity sites was cooperative, native thin filament troponin was exchanged with troponin labeled on troponin C with 2-(4'-iodoacetamidanilo)naphthalene-6-sulfonic acid. From the Ca2+-sensitive fluorescence of this complex, Ca2+ binding was cooperative with a Hill coefficient of 1.7-2.0. Using the troponin-exchanged thin filaments, myosin subfragment 1 MgATPase rate activation was also cooperative and closely proportional to Ca2+ thin filament binding. Reconstitution of the thin filament from its components raised the Ca2+ affinity by a factor of 2 (compared with native thin filaments) and incorporation of fluorescently modified troponin raised the Ca2+ affinity by another factor of 2. Stoichiometrically reconstituted thin filaments produced non-cooperative MgATPase rate activation, contrasting with cooperative activation with native thin filaments, troponin-exchanged thin filaments and thin filaments reconstituted with a stoichiometric excess of troponin. The Ca2+-induced fluorescence transition of stoichiometrically reconstituted thin filaments was non-cooperative. These results suggest that Ca2+ binds cooperatively to the regulatory sites of the cardiac thin filament, even in the absence of myosin, and even though cardiac troponin C has only one Ca2+-specific binding site. A theoretical model for these observations is described and related to the experimental data. Well-known interactions between neighboring troponin-tropomyosin complexes are the proposed source of cooperativity and also influence the overall Ka. The data indicate that Ca2+ is four times more likely to elongate a sequence of troponin-tropomyosin units already binding Ca2+ than to bind to a site interior to a sequence of units without Ca2+.

Actins↗
PubMed1990

Laser-assisted vasectomy reversal: experience in 32 patients.

A Food and Drug Administration approved protocol using a microsurgical carbon dioxide laser to assist in vasectomy reversal was instituted in January 1987. Between January 1987 and December 1988 the procedure was performed on 32 patients, 31 of whom submitted sperm and were available to evaluate. Success rates for sperm in the ejaculate in patients who underwent vasectomy less than 10 years previously were excellent, approaching 95%. The pregnancy rate in this group was 35%. In patients whose vasectomy was performed more than 10 years before reversal the results were much poorer. The success rate for sperm in the ejaculate was only 36% and the pregnancy rate was only 9%. The advantage of laser-assisted vasectomy reversal is that it is a simpler technical procedure that requires considerably less time than a 2-layer microsurgical technique. There were no significant complications, sperm granuloma, or even significant swelling or hematoma in any patient operated upon. Laser-assisted vasectomy reversal is at least equal to conventional microsurgical techniques and definitely easier to perform surgically.

Adult↗