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Biomedical subjects

G A Myers

Publications and source records attributed to G A Myers.

At least 19 recordsLinked to original sources
PubMed2001

Sterilizing immunity against experimental Helicobacter pylori infection is challenge-strain dependent.

The development of a murine model of Helicobacter pylori infection through serial in vivo passage of candidate strains has enabled a quantitative assessment of vaccine efficacy. In this study we compare infection with and protection against challenge from both CagA(+) type I, and CagA(-) type II in vivo adapted isolates. In vivo passage of a type II H. pylori isolate resulted in a highly infectious strain (X47-2AL), capable of reproducibly infecting mice to high density (10(7) CFU/g of gastric tissue). Similarly adapted type I strains were found to colonize mice at a significantly lower level (10(4)-10(5) CFU/g tissue). Mucosal immunization with recombinant urease (rUre) significantly protected animals against both types. Protection against X47-2AL was characterized by a > or =100-fold (or 2 log) reduction in bacterial density. However, the presence of a residual infection highlighted the inability to achieve sterilizing immunity against this strain. The level of protection appeared independent of challenge dose, and was stable for up to 6 months, all animals exhibiting a low-level residual infection that did not recrudesce with time. Similarly immunized mice challenged with isolates representing the residual infection were also protected, confirming that they did not represent a sub-population of H. pylori that could escape immunity. Immunization and challenge studies with type I adapted-isolates, demonstrated a similar 2-3 log reduction in the bacterial burden, but that in this instance resulted in sterilizing immunity. These results suggest varied specificity for the murine host by different Helicobacter strains that can influence the outcome of both infection and immunity.

Administration, Oral↗
PubMed1999

Oral immunization with recombinant Helicobacter pylori urease confers long-lasting immunity against Helicobacter felis infection.

Recombinant Helicobacter pylori urease (rUre) has been shown to confer protection against challenge with Helicobacter felis in mice. The purpose of the present study was to examine duration of the immune response and long-term protective efficacy of immunization with rUre. Swiss Webster mice were orally immunized four times at weekly intervals with 100 microg rUre plus 5 microg heat-labile enterotoxin of Escherichia coli (LT) adjuvant, or with LT only. At 4, 10, 20 or 40 weeks post immunization, 25 rUre-immunized mice and control mice were challenged with H. felis and sacrificed at 2 or 10 weeks post-challenge. H. felis infection was assessed by gastric urease assay and by histology. Anti-H. pylori urease specific antibody levels were measured in serum and saliva both pre- and post-challenge. Over the 40 week time period, the infection rates in rUre-immunized mice were significantly lower than those in controls (p < 0.05) as assessed by gastric urease activity. Protection ranged from 79 100% at 2 weeks post-challenge and 63-78% at 10 weeks post-challenge. Gastric bacterial density in rUre-immunized mice was significantly lower than that of controls (p < 0.03) as determined by histologic assessment. Anti-urease antibody levels remained elevated in the serum and mucosal compartments at 39 weeks following immunization. This study shows that immunization with rUre plus LT results in long-lasting protective immunity against challenge with H. felis.

Adjuvants, Immunologic↗
PubMed1998

Immunization of mice with urease vaccine affords protection against Helicobacter pylori infection in the absence of antibodies and is mediated by MHC class II-restricted responses.

We examined the roles of cell- and antibody-mediated immunity in urease vaccine-induced protection against Helicobacter pylori infection. Normal and knockout mice deficient in major histocompatibility complex (MHC) class I, MHC class II, or B cell responses were mucosally immunized with urease plus Escherichia coli heat-labile enterotoxin (LT), or parenterally immunized with urease plus aluminum hydroxide or a glycolipid adjuvant, challenged with H. pylori strain X47-2AL, and H. pylori organisms and leukocyte infiltration in the gastric mucosa quantified. In an adjuvant/route study in normal mice, there was a direct correlation between the level of protection and the density of T cells recruited to the gastric mucosa. In knockout studies, oral immunization with urease plus LT protected MHC class I knockout mice [beta2-microglobulin (-/-)] but not MHC class II knockout mice [I-Ab (-/-)]. In B cell knockout mice [microMT (-/-)], vaccine-induced protection was equivalent to that observed in immunized wild-type (+/+) mice; no IgA+ cells were detected in the stomach, but levels of CD4(+) cells equivalent to those in the wild-type strain (+/+) were seen. These studies indicate that protection of mice against H. pylori infection by immunization with the urease antigen is dependent on MHC class II-restricted, cell-mediated mechanisms, and antibody responses to urease are not required for protection.

Adjuvants, Immunologic↗
PubMed1998

Physiologic evaluation and surgical management of failed ileoanal pouch.

BACKGROUND: Following proctocolectomy and ileal pouch-anal anastomosis, a small percentage of patients will have poor functional results attributable to pouchitis or anastomotic or septic complications. Additionally, functional failures can occur secondary to limited pouch capacity and compliance. We present five such patients managed with operative conversion to W-ileal pouch-anal anastomosis and examined physiologic parameters important for improving functional results. METHODS: Five female patients (mean age, 30 (range, 24-39) years) with poorly functioning J-ileal pouch-anal anastomoses were referred for evaluation with symptoms of high stool frequency and incontinence problems. Three had severe nocturnal incontinence, and the remaining two patients experienced minor nocturnal incontinence. Preoperative and postoperative evaluation included barium pouch studies, flexible sigmoidoscopy, anal manometry, evacuation volume, and pouch compliance. Pouch-to-anal pressure gradients were calculated. To improve reservoir capacity and compliance, all five patients underwent conversion to W-ileal pouch-anal anastomoses. RESULTS: Twenty-four hour and nocturnal stool frequencies decreased from 13.8+/-1.7 and 3+/-1.3 to 5.8+/-0.3 and 0.3+/-0.2 postconversion (P < 0.05). Mean pouch evacuation volume increased from 83+/-27 to 290+/-29 ml postoperatively (P < 0.05). Pouch compliance increased from 2.7+/-0.5 mmHg/ml to 7.7+/-0.6 mmHg/ml postconversion (P < 0.05). Improvement in postconversion stool frequency correlated with an increase in pouch evacuation volume (r=-0.87). All patients reported improved day and nocturnal continence, despite no significant change between preoperative and postoperative anal manometric pressures. Improved continence correlated with a significant widening of the pouch-to-anal pressure gradients, which increased from 5 to 25 mmHg at 150 ml following pouch conversion. CONCLUSIONS: Poorly functioning ileal reservoirs secondary to limited capacity and compliance can be successfully managed with conversion to W-ileal pouch-anal anastomosis. The increased pouch capacity is associated with improvement in compliance and widening of the pouch-to-anal pressure gradients, providing excellent functional results.

Adult↗
PubMed1998

Rectal and intranasal immunizations with recombinant urease induce distinct local and serum immune responses in mice and protect against Helicobacter pylori infection.

To determine the optimal inductive sites for immunization against Helicobacter pylori infection, the protective efficacy of recombinant urease (rUre) was assessed for mice given the vaccine by either the oral (p.o.), intranasal (i.n.), or rectal route. When mice were immunized with rUre (25 microg p.o. or rectally or 10 microg i.n.) plus heat-labile toxin from Escherichia coli as the mucosal adjuvant, all routes afforded protection against challenge with H. pylori, as indicated by a significant reduction in gastric urease activity (P < 0.0005) compared to that of sham-immunized controls. Quantitative H. pylori culture of stomach tissue demonstrated a >97% reduction in bacterial burden in mice immunized by all routes (P < 0.05). Induction of antiurease immunoglobulin A (IgA) levels in gastric luminal secretions after p.o. immunization was greater than after i.n. administration (means, 6.0 and 1.02 ng/ml, respectively) and was dependent upon challenge with H. pylori. However, immunization by the rectal route resulted in the generation of the highest levels of gastric antiurease IgA (mean, 40. 89 ng/ml), which was detectable prior to challenge with H. pylori. Immunohistochemical staining of stomach tissue for cells secreting urease-specific antibody and CD4(+) T cells showed levels of recruitment to be dependent upon challenge with H. pylori and equivalent for all routes. These results identify both the rectum and nasal passages as suitable inductive sites for urease immunization.

Administration, Intranasal↗
PubMed1998

Filtration of diaspirin crosslinked hemoglobin into lung and soft tissue lymph.

Diaspirin crosslinked hemoglobin (DCHb) is a new blood substitute manufactured from human blood. To evaluate its microvascular filtration properties, we infused DCLHb into unanesthetized sheep (10%, 20 ml/kg) and measured the flow and composition of lung and soft tissue lymph. For comparison, we also infused human serum albumin (HSA; 10%, 20 ml/kg). DCLHb raised systemic and pulmonary arterial pressures from baseline values of 83 +/- 7 and 13 +/- 2 mm Hg, respectively, to peak values of 113 +/- 9 and 26 +/- 3 mm Hg (p < 0.05 versus baseline). These increases were significantly greater than those associated with HSA, which raised systemic and pulmonary arterial pressures from baseline values of 86 +/- 4 and 13 +/- 2 mm Hg, respectively, to peak values of 97 +/- 3 and 21 +/- 7 mm Hg (p <= 0.05 versus baseline and versus DCLHb). These differences reflect the known pressor properties of DCLHb. Accordingly, DCLHb raised lung and soft tissue lymph flows to peak values of 12.2 +/- 3.8 and 1.6 +/- 0.7 ml/30 min, respectively, while HSA raised lung and soft tissue lymph flows to peak values of 7.5 +/- 4.8 and 4.6 +/- 1.9 ml/30 min, respectively (p <= 0.05 versus DCLHb). The half-times of DCLHb equilibration from plasma into lung and soft tissue lymph of 1. 0 +/- 0.3 and 2.1 +/- 1.1 h, respectively, were significantly faster than HSA equilibration half-times of 3.1 +/- 0.2 and 3.8 +/- 0.9 h. Filtration differences between DCLHb and HSA appear to be due to the pressor properties DCLHb.

Animals↗
PubMed1997

Pneumocystis carinii pneumonia postrestorative proctocolectomy for ulcerative colitis: a role for perioperative prophylaxis in the cyclosporine era? Report of a case and review of the literature.

PURPOSE: Medical management of severe ulcerative colitis has used cyclosporine with increasing frequency as an adjuvant to systemic steroids and mercaptopurine. However, the effects of combined management with cyclosporine and prednisone may lead to significant immune compromise and adversely affect operative morbidity in the event urgent surgery is required. METHODS: A case is reported of a 43-year-old white male who presented with severe ulcerative colitis. The patient had been initially treated with prednisone and cyclosporine for six weeks before surgical intervention. The intractability of his ulcerative colitis caused the patient to present to surgery, where he underwent restorative proctocolectomy. RESULTS: On initial presentation, the patient manifested systemic signs of severe ulcerative colitis with hypoalbuminemia, anemia, and weight loss, despite continuous prednisone and cyclosporine management. Before surgical intervention, a chest x-ray and the patient's respiratory status were normal. A total abdominal colectomy with ileal pouch reconstruction and temporary loop ileostomy were performed without incident. On the fifth postoperative day, the patient developed respiratory failure, which was subsequently diagnosed as Pneumocystis carinii pneumonia. Although ventilator support and both aggressive medical and surgical management eventually resulted in successful outcome, significant perioperative morbidity occurred. CONCLUSIONS: In the era of aggressive medical management for ulcerative colitis with both steroids and cyclosporine, the complications of immunosuppression may be significant, including opportunistic pneumonia. Prophylaxis against P. carinii pneumonia with sulfa antibiotics should be considered, especially in patients for whom proctocolectomy is a potential end point.

Adult↗
PubMed1997

Gastritis in urease-immunized mice after Helicobacter felis challenge may be due to residual bacteria.

BACKGROUND & AIMS: Oral immunization with recombinant Helicobacter pylori urease (rUre) coadministered with a mucosal adjuvant protects mice against challenge with Helicobacter felis. In this study, the duration of protection and gastritis after challenge were characterized at sequential time intervals up to 1 year. METHODS: Outbred Swiss-Webster mice were orally immunized with rUre plus adjuvant and examined for the presence of H. felis infection and leukocyte infiltration into the gastric mucosa. RESULTS: When defined by gastric urease activity, 70%-95% of rUre-immunized mice were protected for between 2 and 57 weeks. Challenge with H. felis increased the inflammatory response in the gastric mucosa of rUre-immunized mice, which also had elevated CD4+ and CD8+ T cells. The CD8+ cells represented a population of gastric intraepithelial cells, which expressed the mucosal alpha E-integrin. Epithelial changes consisting of parietal cell loss and hyperplasia of the epithelium occurred in approximately 20% of the mice. Antimicrobial triple therapy significantly decreased the degree of gastritis and epithelial alteration in the stomach. CONCLUSIONS: These results indicate that oral immunization of mice with rUre produces a long-lasting inhibition of H. felis infection but that residual bacteria may produce a persistent lymphocytic infiltration under these experimental conditions.

Animals↗
PubMed1997

Lung lymph oncotic pressure may not modulate pulmonary vascular filtration in sheep.

We tested the hypothesis that plasma oncotic pressure alone, not the plasma-to-lymph oncotic pressure difference, modulates pulmonary transvascular fluid filtration. To do this we measured lung lymph flow after raising left atrial pressure (by inflating a balloon) in sheep that were receiving a continuous (32 h) infusion of dextran 40. For comparison, we also raised left atrial pressure elevation, plasma oncotic pressures in dextran and control sheep, respectively, were 39.5 +/- 4.5 and 17.7 +/- 2.2 mm Hg; plasma-to-lymph oncotic pressure gradients, respectively, were 4.4 +/- 0.6 and 4.4 +/- 0.6 mm Hg. Left atrial pressure elevation during dextran infusion increased lung lymph flow by a factor of 2.4 +/- 0.4, compared with a factor of 4.2 +/- 2.3 in control sheep. Thus, left atrial pressure elevation increased lymph flow less in dextran-treated animals than in control animals, even though the plasma-to-lymph oncotic pressure gradients were equal. This suggests that plasma oncotic pressure alone may be a more important determinant of pulmonary transvascular fluid filtration than the plasma-to-lymph oncotic pressure difference.

Animals↗
PubMed1996

Pulmonary vascular filtration of starch-based macromolecules: effects on lung fluid balance.

BACKGROUND: Pulmonary edema is a complication of critical care fluid management that may be restricted by the use of oncotically effective resuscitation fluids. Potentially beneficial oncotic properties of starch-based plasma volume expanders such as hetastarch (Het), pentafraction (Pen), and Dextran-70 (Dex) may be compromised by their broad range of molecular masses, some of which are small enough to filter from the circulation. Leakage of these molecules into the pulmonary interstitium may limit their oncotic effectiveness and enhance fluid filtration. We measured the filtration of these three resuscitation solutions into lung lymph to evaluate their oncotic contribution to pulmonary edema formation. MATERIALS AND METHODS: Unanesthetized euvolemic adult sheep, prepared with chronic lung lymph fistulae, underwent plasma volume expansion with Het (n = 6), Pen (n = 6), or Dex (n = 6 ) (6%, 35 ml/kg/90 min). Oncotic effectiveness was determined by measuring plasma and lymph oncotic pressures and the oncotic pressures contributed by each starch. Pulmonary hydrostatic pressures and lung lymph flows (Q(L)) were also measured. Results are expressed as means +/- SEM. Comparisons were made by two-factor analysis of variance. RESULTS: Dex contributed 9.0 +/- 0.9 mmHg to the plasma oncotic pressure, significantly more than Het and Pen (5.3 +/- 0.6, 6.5 +/- 0.6 mmHg, respectively). However, Dex filtration also contributed 6.1 +/- 0.5 mmHg to the lymph oncotic pressure, compared to 3.1 +/- 0.3 and 4.7 +/- 0.5 mmHg for Het and Pen, respectively (P < or = 0.05). Dex, Het, and Pen raised Q(L) over baseline by 7.7 +/- 1.5, 4.3 +/- 1.0, and 3.2 +/- 0.7 ml/30 min, respectively (P < or = 0.05). Dex increased Q(L) significantly more than Het or Pen. CONCLUSIONS: Pen and Het demonstrated greater oncotic effectiveness because of restricted plasma-to-lymph macromolecular filtration and limited transvascular fluid flux. By comparison, Dex filtered rapidly and increased transvascular fluid filtration. Pen appears to possess filtration properties that optimize critical care fluid management compared to currently available colloid solutions such as Het and Dex.

Animals↗
PubMed1995

Management of paraesophageal hernia with a selective approach to antireflux surgery.

BACKGROUND: The role of an antireflux procedure in the management of paraesophageal hernia is controversial. To address this issue, we reviewed our experience with selective use of antireflux procedures in patients with pure paraesophageal hernia (type II; n = 26) and those with a partial sliding component (type III; n = 11). PATIENTS AND METHODS: Surgical repair was performed on diagnosis in all 37 patients. Competency of the lower esophageal sphincter was evaluated on the basis of reflux symptoms, and objectively, with endoscopy in 21 patients and 24-hour esophageal pH studies in 17 patients. Repair included an antireflux procedure in 11 patients, as indicated by reflux disease. RESULTS: Preoperatively, 80% of both type II and type III patients reported obstructive symptoms. Reflux symptoms were present in 27% of patients--19% of type II and 45% of type III patients. Endoscopy revealed esophagitis in 5 cases, and 24-hour pH studies indicated significant reflux in 3 of 17 patients. There were no operative deaths and 1 recurrence. Symptoms improved in 92% of patients after surgery. Medically manageable reflux was identified in 2 patients. CONCLUSIONS: Frequent obstructive symptoms and the potential for gastric volvulus indicate elective repair of paraesophageal hernia on diagnosis. Significant gastroesophageal reflux is less common, especially in type II patients, and excellent symptomatic results are obtained with selective application of an antireflux procedure.

Adult↗
PubMed1995

Effects of pentafraction and hetastarch plasma expansion on lung and soft tissue transvascular fluid filtration.

BACKGROUND: Hetastarch and pentafraction are high molecular weight starch solutions designed to augment plasma oncotic pressure. Although clinical utilization of hetastarch has been limited by reported coagulation abnormalities, pentafraction is a newer derivative that appears to have few adverse hemostatic effects. We examined the ability of pentafraction to modulate lung and soft tissue transvascular fluid filtration under hypoproteinemic conditions compared with hetastarch and Ringer's lactate (LR). METHODS: Awake, protein-depleted sheep (n = 19) were prepared with lung and soft tissue lymph fistulas, and comparable infusions of 5% pentafraction (n = 6), 6% hetastarch (n = 6), or LR (n = 7) were administered. Plasma and lymph samples were collected during 24-hour period to determine changes in protein concentrations, plasma-to-lymph oncotic gradients, and lung (QL) and soft tissue (QS) lymph flows. RESULTS: QL and QS rose nearly twofold after protein depletion alone. LR infusion increased QL and QS to 8.7 +/- 1.7 and 3.1 +/- 0.6 times normoproteinemic baseline, respectively (p < 0.05). In contrast, hetastarch and pentafraction infusion limited the increase in QL to 4.2 +/- 1.1 and 4.0 +/- 0.8 times normoproteinemic baseline, respectively (p < 0.05 versus LR) and did not significantly increase QS. Hetastarch and pentafraction infusions increase plasma oncotic pressure by nearly 6 mm Hg, which significantly widened the plasma-to-lymph oncotic pressure gradients above preinfusion baseline by 4.7 +/- 0.7 and 3.4 +/- 0.4 mm Hg in lung and 4.6 +/- 0.7 and 3.2 +/- 0.4 mm Hg in soft tissue, respectively (p < 0.05). CONCLUSIONS: Both hetastarch and pentafraction limit transvascular fluid filtration under hypoproteinemic conditions by augmenting plasma oncotic pressure and the plasma-to-lymph oncotic pressure gradient. Because of fewer adverse hemostatic effects pentafraction may be an improvement over current therapies in critical care fluid management.

Animals↗
PubMed1995

Spectral analysis of arterial pressure lability in rats with sinoaortic deafferentation.

Traditionally, the standard deviation (SD) of the mean arterial pressure (AP) has been used as an index for the AP lability produced by interruption of baroreceptor afferents. Although a useful measure of variance about the mean, the SD does not provide any information about the temporal characteristics of this variability. We employed two different spectral analytic techniques to characterize AP waveforms in rats with sinoaortic deafferentation (SAD) and in sham-operated (Sham) rats to determine if the AP waveform in SAD animals was qualitatively and/or quantitatively different from that of Sham animals. The SAD and Sham animals exhibited qualitatively different spectral profiles, suggesting that lability of AP in SAD animals is not simply an exaggeration of normal fluctuations. In addition, a low-frequency (0.3-0.5 Hz) spectral peak was found in Sham but not SAD animals, suggesting that it is associated with the baroreflex. Finally, we observed in both normal rats and rats without intact baroreceptors that the spectral components of AP are not static but rather vary continuously across time.

Afferent Pathways↗
PubMed1994

Management of fulminant ulcerative colitis by primary restorative proctocolectomy.

UNLABELLED: Severe acute ulcerative colitis unresponsive to medical management is characterized by multiple associated risk factors including anemia, hypoproteinemia, and high steroid requirements when urgent surgery is required. Current surgical options include use of primary ileal pouch-anal anastomosis (IPAA) vs. historic trends favoring colectomy with ileostomy. PURPOSE: To evaluate the efficacy of primary IPAA in patients with severe colitis, we reviewed our own experience in 20 patients with this condition. METHODS: Patients undergoing primary restorative proctocolectomy included 13 males and 7 females (mean age, 30.5 +/- 2.4 years). Exclusion criteria for primary reconstruction included septic patients and patients with associated medical conditions such as pulmonary or cardiovascular disease. History of ulcerative colitis averaged 3.1 +/- 1.1 years (range, 1 month to 19 years). Preoperative mean total serum protein concentration was 5.0 +/- 0.2 g/dl, and mean albumin concentration was 2.1 +/- 0.2 g/dl, reflecting disease severity. The average daily steroid requirement at the time of urgent colectomy was 58.0 +/- 4.4 mg of prednisone (or intravenous equivalent). Primary IPAA included 18 "W" reservoirs, 1 "S" reservoir, and 1 "J" reservoir. RESULTS: Major surgical complications included mild pancreatitis (10 percent), anastomotic leak (5 percent), adrenal insufficiency (15 percent), an upper gastrointestinal bleed (5 percent), and small bowel obstruction (15 percent). There were no deaths, and no patients developed pelvic sepsis or required IPAA removal. At three and twelve months, 24-hr stool frequency averaged 7.3 +/- 0.4 and 4.9 +/- 0.3, respectively. Overall day and night continence was excellent and not different from patients who underwent elective IPAA procedures for ulcerative colitis. CONCLUSIONS: Improved options such as primary IPAA may be safely used in selected patients requiring urgent surgery for severe or fulminant ulcerative colitis. Medical management should be abbreviated when disease control cannot be promptly achieved.

Acute Disease↗
PubMed1993

Level dependent signal flow in the light pupil reflex. I. Latency of time domain responses to transient stimuli.

Latency of pupillary responses to light stimuli are smaller for larger steps of light, and larger for smaller steps of light (Alpern 1954; Lowenstein et al. 1964; Lee et al. 1969; Terdiman et al. 1969; Cibis et al. 1977; and many others). Miller and Thompson (1978), however, reported negligible change in pupil cycle time (period of high gain instability oscillations) with increased mean brightness. Sandberg and Stark (1968) reported a negligible reduction in phase lag of pupillary responses to sinusoidal light stimuli as the modulation coefficient (m) increased. To resolve the inconsistency between the well-documented dependence of latency upon brightness, and the apparent absence of level dependence in the phase characteristics (as reflected directly in the responses to sinusoidal stimuli and indirectly in pupil cycle time experiments) we measured: 1. Latency to step stimuli of light, 2. Phase of responses to sinusoidal light stimuli and 3. Period (pupil cycle time) of high gain instability oscillations. The dependence of pupillary latency upon stimulus level (both light and accommodation) and the interaction between accommodation and light responses were investigated. We show that most of the level dependence of light-pupil latency resides in the afferent path. In the companion papers, we demonstrate that: 1. Phase of pupillary response to sinusoidal light stimuli is reduced by increased mean light level, but is independent of pupil size and accommodative stimulus level; and 2. The period of high gain oscillations is shown to decrease with increased mean light level.(ABSTRACT TRUNCATED AT 250 WORDS)

Accommodation, Ocular↗
PubMed1993

Level dependent signal flow in the light pupil reflex. II. Phase velocity of responses to sinusoidal light stimuli.

Pupillary responses to sinusoidal light stimuli were measured over a range of light levels and frequencies. The phase lag and equivalent time delay of these responses were reduced in an approximately log-linear fashion with increasing mean light level (slope = -60 ms/log unit). The magnitude of this level dependence is reduced at higher frequencies, and at higher light levels. This nonlinear level dependent signal flow (LDSF) effect is shown to be essentially independent of target distance (accommodative stimulus) which influences pupil size, and of pupil size itself. Thus most of the level dependence probably resides in the afferent path of the light-pupil reflex arc, before the accommodation signal joins the light signal in the Edinger-West-phal nucleus. A systems model is presented to the LDSF effect described here and in the companion papers (Myers and Stark 1993a, b). When parameters of the model are adjusted to fit pupillary responses to transient light stimuli over a range of light levels, the model simulates reduced phase lag in response to increased mean light level, and the reduction in this LDSF effect with increased mean light level or increasing stimulus frequency without further changes in parameters. This latter reduction explains the relatively small level dependence seen in latency data (-34 ms/log unit). These data will be shown (Myers and Stark 1990b) to be commensurate with reduction in pupil cycle time (increased frequency of oscillation) observed in high gain oscillation experiments as mean brightness increases.(ABSTRACT TRUNCATED AT 250 WORDS)

Accommodation, Ocular↗
PubMed1993

Level dependent signal flow in the light pupil reflex. III. Phase velocity in high gain instability oscillations.

The pupil can be excited to sustained oscillations under high gain feedback conditions. The period of these oscillations (cycle time) is reduced by increased average light level by an amount commensurate with reductions in phase lag reported in the companion paper (Myers et al. 1991b). A mathematical model of this phenomenon is used to unify and clarify experimental data presented here and in the literature.

Cybernetics↗