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S Siegel

Publications and source records attributed to S Siegel.

At least 19 recordsLinked to original sources

Effect of hydroxyl group position and system parameters on the features of hydroxystearic Acid monolayers.

The characteristic features of hydroxystearic acid monolayers OH-substituted in the mid position of the alkyl chain deviate considerably from those of the usual nonsubstituted stearic acid. The phase behavior, domain morphology, and two-dimensional lattice structure of 9-, 11-, and 12-hydroxystearic acids are studied, using pi-A isotherms, Brewster angle microscopy (BAM), and grazing incidence X-ray diffraction (GIXD), to obtain detailed information on the effect of the exact position of the OH-substitution. The pi-A isotherms of all three hydroxyoctadecanoic acids have an extended flat plateau region, the extension of which only slightly decreases with the increase of temperature. At the same temperature, the extension of the plateau region increases and the plateau pressure decreases from 9-hydroxyoctadecanoic acid to 12-hydroxyoctadecanoic acid. The absolute -DeltaH and -DeltaS values for the phase transition increase slightly from 9-hydroxyoctadecanoic acid to 12- hydroxyoctadecanoic acid and indicate differences in the ordering of the condensed phase under consideration of the special reorientation mechanism of these bipolar amphiphiles at the fluid/condensed phase transition. The morphology of the condensed phase domains formed in the fluid/condensed coexistence region is specific for the position of the OH-substitution of the alkyl chain, just as the lattice structures of the condensed monolayer phase. 11-hydroxyoctadecanoic acid monolayers form centered rectangular lattices with the chain tilt toward the NNN (next nearest neighbor) direction, and 12-hydroxyoctadecanoic acid monolayers have an oblique lattice over the entire pressure range. A special feature of 9-hydroxystearic acid monolayers is the phase transition between two condensed phases observed in the pi-A isotherm of 5 degrees C at approximately 18 mN/m, where the centered rectangular lattice shows a NNN/NN transition. The morphology of the condensed phase domains formed in the fluid/condensed coexistence region, just as the lattice structures of the condensed monolayer phase, reveal the high specifity of the monolayer feature of the bipolar hydroxystearic acids OH-substituted in the mid position.

Journal Article↗

Urinary retention after tension-free vaginal tape procedure: incidence and treatment.

OBJECTIVES: To review our experience with persistent urinary retention after the tension-free vaginal tape (TVT) procedure and report our treatment results. Ulmsten recently introduced the TVT procedure for female stress urinary incontinence. Although the morbidity is minimal, no surgical procedure is without risks, and experience will better define the morbidity of the TVT procedure. METHODS: Since November 1998, we have collectively performed 600 TVT procedures. Of these, 17 patients (2.8%) developed urinary retention or symptoms consistent with obstruction (including hesitancy, straining to void, or feeling of incomplete emptying) lasting more than 1 week from the date of the procedure. We reviewed the operative record, noting the operative time, estimated blood loss, presence of bladder penetration, and any reported complications. All 17 patients subsequently underwent transvaginal release on an outpatient basis. RESULTS: Seventeen patients (mean age 56 years, range 38 to 81) underwent sling release a mean of 64 days (range 6 to 228) after the TVT procedure. All patients voided to completion within 24 hours of release and reported no further subjective complaints of outlet obstruction. None of the subjects reported de novo urge incontinence or urgency. In each patient, the estimated blood loss was minimal; the operative time averaged 15 minutes. One urethral injury occurred and was managed intraoperatively without sequelae. Sixteen patients who underwent sling release have remained dry; the remaining patient, in whom a urethral injury was repaired, redeveloped stress incontinence and underwent an uncomplicated successful transvaginal sling procedure. CONCLUSIONS: Outlet obstruction is a risk of the TVT procedure and occurred with an incidence of 2.8% in our experience. The TVT mesh can be released by a simple vaginal incision under local anesthesia with rapid return to normal voiding. Although the number of patients studied was small, stress incontinence did not recur after uncomplicated release in our series.

Adult↗

The role of cholecystokinin in conditional compensatory responding and morphine tolerance in rats.

As elaborated in the conditioning analysis of tolerance, cues present at the time of drug administration become associated with the drug effect. A particularly salient cue that may become associated with the drug effect is the pharmacological drug-onset cue inherent to drug administration. Drug-associated cues contribute to tolerance by eliciting a conditional compensatory response that attenuates the drug effect. For example, the early drug effect, having been paired with the subsequent larger drug effect, may elicit the release of antiopioid peptides that counter opioid effects. The role of a putative antiopioid peptide, cholecystokinin-8 (CCK), in the associative mechanisms of opiate tolerance was evaluated. The results of these experiments suggest that a CCK2 receptor antagonist attenuates both the expression of opiate tolerance and the conditional compensatory response hypothesized to mediate such tolerance.

Animals↗

Performance evaluation of the microPET P4: a PET system dedicated to animal imaging.

The microPET Primate 4-ring system (P4) is an animal PET tomograph with a 7.8 cm axial extent, a 19 cm diameter transaxial field of view (FOV) and a 22 cm animal port. The system is composed of 168 detector modules, each with an 8 x 8 array of 2.2 x 2.2 x 10 mm3 lutetium oxyorthosilicate crystals, arranged as 32 crystal rings 26 cm in diameter. The detector crystals are coupled to a Hamamatsu R5900-C8 PS-PMT via a 10 cm long optical fibre bundle. The detectors have a timing resolution of 3.2 ns, an average energy resolution of 26%, and an average intrinsic spatial resolution of 1.75 mm. The system operates in 3D mode without inter-plane septa, acquiring data in list mode. The reconstructed image spatial resolution ranges from 1.8 mm at the centre to 3 mm at 4 cm radial offset. The tomograph has a peak system sensitivity of 2.25% at the centre of the FOV with a 250-750 keV energy window. The noise equivalent count rate peaks at 100-290 kcps for representative object sizes. Images from two phantoms and three different types of laboratory animal demonstrate the advantage of the P4 system over the original prototype microPET. including its threefold improvement in sensitivity and a large axial FOV sufficient to image an entire mouse in a single bed position.

Animals↗

Self-administration cues as signals: drug self-administration and tolerance.

There is evidence that drug-associated exteroceptive cues elicit compensatory conditional responses (CCRs) that contribute to tolerance. The authors evaluated whether interoceptive, self-administration cues (SACs) similarly contribute to tolerance. In Experiments 1 and 2, the ataxic effect of ethanol was measured in rats that self-administered (SA) ethanol--by either oral consumption or intragastric infusion--and in rats that were yoked (Y) to these self-administrators. In both experiments, the ataxic effect of ethanol was more pronounced in Y than in SA rats. In addition, SA rats failed to display usual levels of tolerance when ethanol was administered in the absence of SACs and displayed a CCR of hypertaxia in response to SACs not followed by ethanol. The results of Experiment 3 indicate that the ataxic effect of intravenous heroin also was greater in Y than in SA rats. The findings suggest that SACs contribute to drug tolerance.

Animals↗

Collagen implant for treating stress urinary incontinence in women with urethral hypermobility.

PURPOSE: We evaluated the use of collagen in women with stress urinary incontinence and urethral hypermobility. MATERIALS AND METHODS: We treated 90 patients with stress urinary incontinence and urethral hypermobility with 1 to 3 injections of Contigen implant (C. R. Bard, Inc., Covington, Georgia) between June 1996 and October 1998. Observations at 3, 6 and 12 months included continence grade, 7-day voiding diaries and quality of life questionnaires. Abdominal leak point pressure was determined at baseline and 12 months. RESULTS: At the 6-month followup 68 patients remained in the study, of whom 30 (44%) were dry and 24 (35%) were improved. Of the 58 patients who reached the 12-month followup 19 (33%) were dry and 19 (33%) were improved. Considering all patients entered into the study at 6 months 30 (33%) were dry and 24 (27%) were improved. Of the original 90 patients 19 (21%) were dry and 19 (21%) were improved at 12 months. The probability of maintaining initial improvement for 12 months was 44%. The success of bulking agent therapy was not predicted by the initial incontinence grade. Improved continence grade correlated with improved leak point pressure. CONCLUSIONS: This therapy is appropriate in women with urethral hypermobility who wish to avoid surgical risks and in those in whom surgery is ill advised.

Adult↗

Sacral nerve stimulation in patients with chronic intractable pelvic pain.

PURPOSE: Transforamenal sacral nerve stimulation with an implantable neuroprosthetic device has been shown to benefit patients with chronic voiding dysfunction. In this study we measured the effectiveness of sacral nerve stimulation in 10 patients with chronic intractable pelvic pain. MATERIALS AND METHODS: After successful percutaneous trial stimulation, a neuroprosthetic sacral nerve stimulation device was surgically implanted in 10 patients with chronic intractable pelvic pain. Leads were placed in the S3 and S4 foramen in 8 and 2 cases, respectively. Patients were evaluated throughout the study using a patient pain assessment questionnaire on a scale of 0-absent to 5-excruciating pain. Pain was assessed at baseline, during test stimulation, and 1, 3 and 6 months after surgical lead implantation. An additional long-term assessment was done at a median followup of 19 months. RESULTS: Of the 10 patients with the implant 9 had a decrease in the severity of the worst pain compared to baseline at a median followup of 19 months. The number of hours of pain decreased from 13.1 to 6.9 at the same followup interval. There was also an average decrease in the rate of pain from 9.7 at baseline to 4.4 on a scale of 10-always to 0-never having pain. At a median of 19 months 6 of 10 patients reported significant improvement in pelvic pain symptomology. CONCLUSIONS: These data imply that transforamenal sacral nerve stimulation can have beneficial effects on the severity and frequency of chronic intractable pelvic pain. Future clinical studies are necessary to determine the long-term effectiveness of this therapy.

Adult↗

Pesticide exposures in children with non-Hodgkin lymphoma.

BACKGROUND: The association between pesticide exposure and non-Hodgkin lymphoma (NHL) in adults has been the subject of numerous case-control and cohort studies. However, to the authors' knowledge, data regarding pesticide exposures in children diagnosed with NHL have been lacking. METHODS: The Children's Cancer Group conducted a study comparing 268 children who developed NHL or leukemia with bulk disease with a group of matched, randomly selected regional population controls. The telephone interviews of both the case and control mothers included selected questions regarding occupational and home exposures to pesticides around the time of the index pregnancy and exposure of the child. RESULTS: A significant association was found between risk of NHL and increased frequency of reported pesticide use in the home (odds ratio [OR] = 7.3 for use most days; trend P = 0.05), professional exterminations within the home (OR = 3.0; P = 0.002), and postnatal exposure (OR = 2.4; P = 0.001). Elevated risks were found for T-cell and B-cell lymphomas; for lymphoblastic, large cell, and Burkitt morphologies; and in both young (age < 6 years) and older children. There was an increased risk of NHL with occupational exposure to pesticides (OR = 1.7) that was not significant overall, but that was significant for Burkitt lymphoma (OR = 9.6; P < 0.05). CONCLUSIONS: The results of the current study provide further evidence linking pesticide exposure to the risk of NHL, but the authors were unable to implicate any specific agent.

Adolescent↗

(AC)23 [Z-2] polymorphism of the aldose reductase gene and fast progression of retinopathy in Chilean type 2 diabetics.

A recent case-control study suggests that the allele (AC)23 of a variable number tandem repeat (VNTR) associated to the aldose reductase (ALR2) gene could be related to early retinopathy in Type 2 diabetics. By means of a longitudinal-retrospective study, we aimed to seek for a relationship between the rate of progression of retinopathy and the (AC)23 allele of the VNTR associated to the ALR2 gene. A random sample was obtained of 27 Type 2 diabetics (aged 68.1 +/- 10.6 years, diabetes duration = 20.7 +/- 4.8 years, mean HbA1 = 10.6 +/- 1.6%). The mean HbA1 was the arithmetic average of 2.2 measurements per patient per year of total glycosilated hemoglobin (Gabbay method, normal range: 4.2-7.5%). Retinopathy was graded by an Ophthalmologist in a scale from zero to four score points. The genotype of the (AC), VNTR was determined by 32P-PCR plus sequenciation in a Perkin-Elmer laser device. The Mann-Whitney test and either chi2 or Fisher's exact test were used. A P < 0.05 was considered as statistically significant. The retinopathy progression rate (RPR, points x year(-1)) was calculated by dividing the increment of retinopathy score (delta Retinopathy Score, [points]), by the duration of the follow up [years]. The 12 diabetics having the (AC)23 allele had a mean RPR 8.9 times higher (0.40 +/- 0.61 points x year(-1)) than the 15 patients who had alleles other than (AC)23 (0.045 +/- 0.099 points x year(-1), P = 0.037). Both groups were similar with respect to: mean HbA1 (10.5 +/- 1.4 and 10.7 +/- 1.7%, P = 0.95), age at diagnosis (48.5 +/- 6.3 and 46.3 +/- 14.0 years, P = 0.81), diabetes' duration (21.3 +/- 4.7 and 20.2 +/- 4.9 years, P = 0.41) and serum creatinine (0.89 +/- 0.2 and 1.13 +/- 0.5 mg dl(-1), P = 0.35). We concluded that, in Type-2 diabetics having similar glycemic control, the (AC)23 allele of the VNTR associated to the ALR2 gene, is associated to a 8.9 times faster progression of retinopathy than in patients who have other alleles.

Age of Onset↗

The role of formalin-induced pain in morphine tolerance, withdrawal, and reward.

The effect of a commonly used experimental pain-induction procedure (formalin injection into a hindpaw site) on morphine tolerance, withdrawal, and reward was examined in rats. Results suggest that the effects of morphine are different in the organism that is experiencing pain at the time it receives the drug than in the organism that is pain free. The presence of pain at the time of each morphine administration decreased analgesic tolerance, decreased naloxone-precipitated withdrawal, and enhanced the rewarding effect of the opiate. These findings, together with those of previous studies, suggest that theories of opiate tolerance, withdrawal, and reward should incorporate the effects of pain.

Analgesics, Opioid↗

Pavlovian psychopharmacology: the associative basis of tolerance.

The Pavlovian conditioning analysis of drug tolerance emphasizes that cues present at the time of drug administration become associated with drug-induced disturbances. These disturbances elicit unconditional responses that compensate for the pharmacological perturbation. The drug-compensatory responses eventually come to be elicited by drug-paired cues. These conditional compensatory responses (CCRs) mediate tolerance by counteracting the drug effect when the drug is administered in the presence of cues previously paired with the drug. If the usual predrug cues are presented in the absence the drug, the unopposed CCRs are evident as withdrawal symptoms. Recent findings elucidate intercellular and intracellular events mediating CCRs and indicate the importance of internal stimuli (pharmacological cues and interoceptive cues inherent in self-administration) to the acquisition of drug tolerance and the expression of withdrawal symptoms.

Animals↗

Onset and duration of action of levocabastine nasal spray in atopic patients under nasal challenge conditions.

BACKGROUND: Although prior studies have documented the rapid onset of action of topical intranasal levocabastine (LEV), little is known about its duration of action under nasal challenge conditions. OBJECTIVES: We sought to assess the onset and duration of action of escalating doses of LEV nasal spray by using a nasal allergen challenge (NAC) model. METHODS: Eighteen asymptomatic subjects with histories of seasonal allergic rhinitis were enrolled into a randomized, single-blind, placebo-controlled, dose-ranging crossover study. Each patient was randomly assigned to receive single doses of placebo and intranasal LEV 0.1, 0.2, and 0.4 mg during 2 parts of the study. In part 1 (onset of action), NAC consisted of a single dose of allergen administered 5 minutes after study drug treatment. In part 2 (duration of action), NAC consisted of increasing doses of allergen administered 0.5, 6, 12, and 24 hours on separate days after study drug treatment. Nasal symptom scores (NSSs) and nasal peak expiratory flow rates were measured after NAC in both phases of the study. Blood samples for plasma LEV concentrations were drawn after each NAC. RESULTS: In part 1, NSSs were significantly lower after the administration of LEV 0.1, 0.2, and 0.4 mg compared with placebo (P <.05). In part 2, NSSs were significantly lower after LEV doses of 0.2 and 0.4 mg compared with placebo at 0.5, 6, 12, and 24 hours after treatment (P <.05). The mean provocative dose of allergen required to elicit a positive nasal reaction was increased after LEV doses of 0.2 and 0.4 mg at 0.5, 6, and 12 hours after treatment. Nasal peak expiratory flow rates demonstrated no significant differences between LEV and placebo for any doses at any time points. Mean plasma LEV concentrations were low (range, 0 to 3. 7 ng/mL) after all doses and did not correlate with drug efficacy. CONCLUSIONS: Single intranasal LEV doses of 0.1, 0.2, and 0.4 mg significantly reduced the severity of the immediate nasal response to allergen when administered 5 minutes before NAC. This protective effect against NAC continued to be present 24 hours after administration of LEV doses of 0.2 and 0.4 mg. Efficacy in blocking the reaction to NAC did not correlate with plasma LEV levels, suggesting that the inhibitory effect was due largely to topical rather than systemic effects.

Administration, Intranasal↗

Drug anticipation and drug addiction. The 1998 H. David Archibald Lecture.

Environmental cues associated with drug use become capable of eliciting withdrawal symptoms, craving and relapse to drug self-administration. The phenomenon, although noted almost 150 years ago, has repeatedly been confirmed in epidemiological and experimental studies. Drug tolerance, which is closely correlated with withdrawal symptoms and craving, is also modulated by drug-associated environmental cues. The contribution of predrug cues to withdrawal and tolerance is emphasized in a Pavlovian conditioning analysis of drug administration. Drug-induced disturbances are modulated by homeostatic responses elicited by pharmacological stimulation. According to the conditioning analysis, we learn to anticipate the drug effect; corrective response (conditional compensatory responses) occur in the presence of situations and events that have been associated with the drug in the past. These conditional responses, seen in anticipation of drugs, importantly contribute to drug tolerance, failures of tolerance (enigmatic overdoses), and withdrawal symptoms. I review evidence indicating that a complete analysis of drug withdrawal and tolerance requires an appreciation of the contribution of Pavlovian conditioning.

Conditioning, Classical↗

Drug-onset cues as signals: intraadministration associations and tolerance.

On the basis of a conditioning analysis of drug tolerance, drug-associated cues become associated with the drug effect. These cues elicit conditional compensatory responses and modulate the expression of tolerance. Although there are many findings consistent with the conditioning analysis of tolerance, there also are contrary findings. The results of these experiments suggest that some of the apparently contradictory findings result because interoceptive pharmacological cues, as well as exteroceptive environmental cues, are paired with a drug effect. That is, within each administration, early drug-onset cues may become associated with the later, larger drug effect, and these pharmacological cues may overshadow simultaneously present environmental cues. We demonstrate the contribution of such intraadministration associations to tolerance to the analgesic effect of morphine and to the expression of conditional compensatory hyperalgesia.

Animals↗