Search PubMed⌕ Search

Biomedical subjects

J Willis

Publications and source records attributed to J Willis.

At least 91 records · Page 5Linked to original sources
PubMed1986

Pharmacokinetics and sputum penetration of ciprofloxacin in patients with cystic fibrosis.

Levels of ciprofloxacin in serum and sputum were studied for eight patients with cystic fibrosis who were infected with Pseudomonas aeruginosa. Patients were studied in a steady state on a dosage of 500 mg every 8 h. Peak levels in serum ranged from 1.27 to 5.6 mg/liter (mean, 3.16 +/- 1.27), and absorption was rapid, the time to peak concentration ranging from 0.5 to 3.0 h (mean, 1.5 +/- 0.9). The antibiotic penetrated sputum well, achieving areas under the curve of approximately 46% of those obtained in serum.

Adolescent↗
PubMed1985

Inhibition of platelet function by contrast media: iopamidol and ioxaglate versus iothalamate. Work in progress.

The effects of an ionic contrast agent, meglumine iothalamate (Conray-60), and two newer low-osmolality radiographic contrast media, sodium meglumine ioxaglate (Hexabrix) and iopamidol (B-15,000), on platelet aggregation and secretion responses were studied. All three agents inhibited platelet responses during stimulation with adenosine diphosphate (ADP), epinephrine, and collagen. Platelet function was inhibited by iothalamate at concentrations of 11 mg iodine/ml and above, and by the newer agents at concentrations above 30 mg iodine/ml. Addition of exogenous calcium decreased the iothalamate-induced inhibition of aggregation but did not improve dense granule secretion. There was no consistent effect of exogenous calcium on platelet inhibition by iopamidol and ioxaglate. These studies indicate that the newer agents inhibit platelet function less than iothalamate does, and that chelation of Ca2+ may not be the major mechanism of platelet inhibition by contrast agents.

Blood Platelets↗
PubMed1984

Platelet-activating factor is a weak platelet agonist: evidence from normal human platelets and platelets with congenital secretion defects.

We have examined the effects of a novel platelet agonist, platelet activating factor (PAF), on human platelets. Irreversible aggregation and 14C-serotonin secretion in response to PAF (10(-5) M) was found to be dependent on both thromboxane production and secreted adenosine diphosphate (ADP). Liberation of arachidonic acid (AA) from membrane-bound phospholipids is a prerequisite step in platelet thromboxane production. Studies with 3H-AA-labeled platelets revealed that PAF (10(-5) M) was a weak stimulus for the mobilization of AA. In addition, PAF (10(-5) M) was found to be a weak inducer of thromboxane synthesis (mean = 6 pmol/10(8) platelets) as compared to thrombin 5 U/ml (mean = 177 pmol/10(8) platelets), measured using a radioimmunoassay for thromboxane B2. Formation of phosphatidic acid is an early step in stimulus-response coupling in platelets. Our studies indicate that PAF is a weak stimulus for phosphatidic acid formation as well. To obtain further insights into its action, we examined the effect of PAF on platelets from three groups of patients with congenital secretion defects: patients with the storage pool deficiency, those with impaired thromboxane synthesis due to impaired liberation of AA from phospholipids, and those with impaired secretion despite normal granule stores and thromboxane production. The response to PAF was impaired in all patients, providing further evidence that PAF-induced platelet activation is dependent on secreted ADP and thromboxane A2 synthesis, and occurs by mechanisms common to a number of agonists. Overall, these studies indicate that PAF is a weak platelet agonist.

Adenosine↗
PubMed1984

Short latency somatosensory evoked potentials in infants.

Short latency somatosensory evoked potentials (SEPs) to unilateral median nerve electrical stimulation were recorded from normal infants at birth and at 2, 4, 6, 8, 10 and 12 months of age. Three channels were recorded: Erb's point-Fz; C II (over 2nd cervical vertebra)-Fz; contralateral C' (2 cm posterior to C3 or C4)-Fz. Sweep time = 50 msec. At birth, the C II potential was seen in all infants; the Erb's point and C' potentials were seen in two-thirds. All older infants had well developed potentials at all sites. The mean latency of the Erb's point potential was stable over time. The latency of the C II potential decreased with maturation. At C', 4 components were seen, the latencies of which decreased with maturation: N1, P1, N2 and P2. The duration of N1 and P1 decreased with maturation. Standard deviations were relatively small for latencies and large for amplitudes. SEPs were adversely affected by using the 60 c/sec filter. Increasing the low frequency filter from 1 to 30 c/sec changed SEP, particularly in younger infants. Abnormal SEPs were seen in prematures surviving periventricular hemorrhage.

Brain↗
PubMed1984

Relapsing polychondritis with multifocal neurological abnormalities.

A sixty-five year old woman developed relapsing polychondritis with three of the diagnostic criteria established by McAdam et al. (1976), namely bilateral auricular chondritis, ocular inflammation and both cochlear and vestibular dysfunction. Many authors have mentioned other neurological symptoms including unilateral facial weakness. This patient is the first case described with bilateral facial weakness and cerebral manifestations. Relapsing polychondritis, an uncommon, recurrent, inflammatory disorder affecting the cartilaginous tissues of the body (Jaksch-Wartenhorst, 1923; Herman, 1981), is regularly associated with audiovestibular dysfunction (Bollet et al., 1969; Cody et al., 1971; McAdam et al., 1976; Ridgway et al., 1979). McAdam et al. (1976) and Ridgway et al. (1979) have mentioned other neurological symptoms including unilateral facial weakness. We recently observed a patient with polychondritis and multifocal neurological abnormalities. We believe this is the first case described with bilateral facial nerve palsy and with cerebral manifestations.

Diabetes Mellitus, Type 2↗
PubMed1984

Platelet secretion defect associated with impaired liberation of arachidonic acid and normal myosin light chain phosphorylation.

We describe four patients with impaired platelet aggregation and 14C-serotonin secretion during stimulation with adenosine diphosphate (ADP), epinephrine, collagen, and platelet-activating factor. The response to arachidonic acid was normal in all patients with regard to aggregation and in three of the four with regard to 14C-serotonin secretion. The total platelet adenosine triphosphate (ATP) and ADP content and the ATP to ADP ratio was normal in all patients, thereby excluding storage pool deficiency as the cause of the secretion defect. Studies with 3H-arachidonic acid-labeled platelets revealed that the thrombin-induced liberation of arachidonic acid from membrane-bound phospholipids was impaired in these patients. Further, platelet thromboxane B2 production, measured using a radioimmunoassay, was diminished during stimulation with ADP and thrombin, but was normal with arachidonic acid, indicating that the oxygenation of arachidonic acid was normal and that the diminished thromboxane production was due to a defect in the liberation of arachidonic acid. Release of arachidonic acid is mediated by phospholipases that are Ca++ dependent. To examine whether these patients may have a defect in making intracellular Ca++ available, another Ca++-dependent process, myosin light chain phosphorylation, was studied during thrombin stimulation. Platelets from three of the patients were found to behave the same as normal ones, suggesting that the deficiency in phospholipase activity may not be due to impaired Ca++ mobilization. Our studies demonstrate a novel group of patients with platelet secretion defects associated with impaired liberation of arachidonic acid from phospholipids. These patients exemplify a congenital defect, other than deficiencies of cyclooxygenase and thromboxane synthetase, by which thromboxane production may be impaired in platelets.

Adenosine Diphosphate↗
PubMed1984

A major role of ADP in thromboxane transfer experiments: studies in patients with platelet secretion defects.

Because of its unstable nature, previous studies of the effect of thromboxane A2 on platelets have been performed by incubating normal platelets with arachidonic acid (generating system) and transferring aliquots of platelet suspensions or their supernates containing thromboxane A2 to indomethacin-treated platelets (recipient system). These studies concluded that thromboxane A2 could induce irreversible aggregation of and 14C-serotonin secretion from the recipient platelets. Our studies indicate that ADP plays a major role in the responses induced by such transferred aliquots in recipient platelets, and that the effects previously attributed solely to thromboxane A2 occur because of a synergism between thromboxane A2 and ADP, which consists of ADP transferred passively and ADP secreted by the recipient platelets. We found optimum dense granule secretion to be dependent on the presence of an intact cyclooxygenase pathway in the recipient platelets and on close cell contact, suggesting that thromboxane A2 may not be as strong an agonist (direct inducer of secretion) as generally considered. Several investigators have performed similar transfer experiments using platelets from patients with secretion defects despite normal granule contents. On the basis of diminished response in the patients' platelets to aliquots of normal platelets stimulated with arachidonic acid, they concluded that the defective platelet secretion was caused by an impaired response to thromboxane A2. Because of the role of ADP demonstrated, we caution against such an inference regarding responsiveness of platelets to thromboxane A2 based purely on the results of the transfer experiments.

Adenosine Diphosphate↗
PubMed1983

Cerebellar lesion in myoclonic encephalopathy of infants.

The syndrome of opsoclonus and polymyoclonus developed in an infant who had acute meningoencephalitis with ataxia. A low-density cerebellar lesion was noted by computed tomography, subsequently resolving with residual cerebellar atrophy. The infant recovered completely, except for a mild intention tremor. This was the first documentation, to our knowledge, of an acute cerebellar lesion in this syndrome.

Cerebellar Ataxia↗
PubMed1983

Inhibition of thromboxane A2 synthesis in human platelets by coagulation factor Xa.

Factor Xa binds to platelets provided that factor Va is present on the platelet surface, an interaction that results in a striking acceleration of the conversion of prothrombin to thrombin. Thrombin then initiates fibrin formation, induces platelet aggregation, and stimulates the intraplatelet synthesis of thromboxane A2 (TXA2). Addition of thrombin (2.4-14.4 nM) to platelet-rich plasma increased the basal level of TXA2, measured as thromboxane B2, from less than 0.5 pmol per 10(8) platelets to (mean +/- SEM) 100 +/- 22 and 250 +/- 10 pmol per 10(8) platelets, respectively. Treatment of platelet-rich plasma with increasing concentrations of factor Xa (1-12 nM) prior to the addition of thrombin progressively inhibited the production of TXA2. Thrombin (9.6 nM), which produced 93% of the maximal formation of TXA2, was inhibited 70% by factor Xa (10 nM). To identify which of these steps in thromboxane synthesis was inhibited by factor Xa, platelets labeled with [14C]arachidonic acid were exposed to thrombin and products of prostaglandin synthesis were separated by thin-layer chromatography. In contrast to the inhibition of TXA2 synthesis, prostaglandin E2 and prostaglandin F2 alpha synthesis were not inhibited suggesting that neither phospholipase(s) nor cycloxygenase was involved. The inhibition of TXA2 formation by factor Xa could be reversed by increasing the molar ratio of thrombin to factor Xa to 5.5. Incubation of platelets with an IgG fraction of a human monoclonal antifactor V antibody, previously shown to inhibit factor Xa binding, was found to block factor Xa inhibition of TXA2 synthesis. The inhibition of TXA2 synthesis requires the presence of the active site serine of factor Xa and is not specific for TXA2 formation induced by thrombin because it is also demonstrable when the agonist is ADP. Further, factor Xa does not require additional plasma components for its action because its inhibitory effects are detected in gel-filtered platelets. The effect of factor Xa was evident at physiological (1.3 mM) calcium concentrations. These results indicate that factor Xa binding to platelets through factor Va not only stimulates thrombin formation but also has a countervailing effect by inhibiting TXA2 formation.

Adenosine Diphosphate↗
PubMed1982

The hemostatic system in children undergoing intensive plasma exchange.

We report the effects on the hemostatic system of intensive plasma exchange therapy using replacement fluids devoid of plasma coagulation proteins. Five children were studied during ten exchanges. There were no hemorrhagic episodes clearly attributable to the plasma exchange, but one patient developed recurrent thrombosis of the vascular access used for the procedure. Plasma values of the various coagulation factors (II to XII) were decreased by 35 to 67% immediately following the plasmapheresis. The mean decrease in levels of antithrombin III antigen and activity and of plasminogen were 58, 60, and 66%, respectively. The recurrent thrombosis of the vascular access in one of the patients, and the decrease in antithrombin III and plasminogen values in plasma following plasmapheresis in all patients, suggest that there is increased potential for thrombosis in patients undergoing intensive plasmapheresis, despite the depletion of coagulation factors. At 24 hours following plasmapheresis the values for all factors were within normal limits, attesting to the ability of the synthetic mechanisms in children to replenish hemostatic factors rapidly.

Adolescent↗
PubMed1982

13C-nuclear magnetic resonance studies of sugar cataractogenesis in the single intact rabbit lens.

In this report we demonstrate that 13C-nuclear magnetic resonance spectroscopy may be used to monitor the sorbitol and glycolytic pathways in a single, intact, crystalline lens of the rabbit, thereby providing a new, noninvasive method for the study of sugar cataractogenesis. This approach is particularly useful for the measurement of intralenticular metabolic fluxes in single lenses under various conditions, at a time resolution previously unavailable in lens biochemistry.

Animals↗