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Biomedical subjects

M Singer

Publications and source records attributed to M Singer.

At least 19 recordsLinked to original sources

Haemodynamic evidence for cardiac stress during transurethral prostatectomy.

OBJECTIVE: To compare haemodynamic performance during transurethral prostatectomy and non-endoscopic control procedures similar in duration and surgical trauma. DESIGN: Controlled comparative study. SETTING: London teaching hospital. PATIENTS: 33 men aged 50-85 years in American Society of Anesthesiologists risk groups I and II undergoing transurethral prostatectomy (20), herniorrhaphy (eight), or testicular exploration (five). MAIN OUTCOME MEASURES: Percentage change from baseline in mean arterial pressure, heart rate, Doppler indices of stroke volume and cardiac output, and index of systemic vascular resistance, and change from baseline in core temperature. RESULTS: In the control group mean arterial pressure fell to 11% (95% confidence interval -17% to -5%) below baseline at two minutes into surgery and remained below baseline; there were no other overall changes in haemodynamic variables and the core temperature was stable. During transurethral prostatectomy mean arterial pressure increased by 16% (5% to 27%) at the two minute recording and remained raised throughout. Bradycardia reached -7% (-14% to 1%) by the end of the procedure. Doppler indices of stroke volume fell progressively to 15% (-24% to -6%) below baseline at the end of the procedure, and the index of cardiac output fell to 21% (-32% to -10%) below baseline by the end of the procedure. The index of systemic vascular resistance was increased by 28% (17% to 38%) at two minutes, and by 46.8% (28% to 66%) at the end of the procedure. Core temperature fell by a mean of 0.8 (-1.0 to -0.6) degrees C. Significant differences existed between the two groups in summary measures of mean arterial pressure (p less than 0.05), Doppler indices of stroke volume (p less than 0.005) and cardiac output (p less than 0.005), index of systemic vascular resistance (p less than 0.0005), and core temperature (p less than 0.0001). CONCLUSIONS: Important haemodynamic disturbances were identified during routine apparently uneventful transurethral prostatectomy but not during control procedures. These responses may be related to the rapid central cooling observed during transurethral prostatectomy and require further study.

Aged

Anomalous effect of mazindol on dopamine uptake as measured by in vivo voltammetry and microdialysis.

The effect of mazindol on the dopamine (DA) uptake system in the rat striatum was studied by in vivo voltammetry and microdialysis. An increase in the maximal uptake rate was observed by voltammetry 30 min after i.p. administration of 1, 5, 10, 15, and 20 mg/kg doses but not after a dose of 25 mg/kg, while stimulated release was enhanced at all doses. The increased maximal uptake is in contrast to increased levels of extracellular DA observed with microdialysis following mazindol administration. This divergence of action is anomalous in the context of current understanding of the DA uptake system.

Animals

Individual differences in bridging inference processes.

The role of individual differences in bridging-inference processing was studied. Students (n = 135) read passages of short to moderate length. After each one, they answered corresponding questions about inferences that bridged causally related ideas that were either near or far apart in the text. The main hypothesis was that local bridging-inference processing is facilitated by the reader's predisposition to access pertinent knowledge during comprehension. Regression analyses provided support for this proposal and indicated that greater working-memory capacity and vocabulary knowledge promote inference processing. The following relationships between the predictors and inference processing were proposed: Knowledge access promotes the co-occurrence in working memory of the text ideas and knowledge needed to compute the bridge. Working-memory capacity enhances the likelihood that needed antecedent ideas will be available to the bridging processes. Vocabulary knowledge may promote inference processing because unfamiliar word meanings place more demands on working-memory resources than do familiar meanings.

Adult

[Grice subtalar arthrodesis: a long-term follow-up in poliomyelitis sequelae].

A retrospective review was done of 19 poliomyelitis feet on which the standard Grice subtalar arthrodesis was performed for correction of valgus feet deformity. The average time of follow-up was 12.1 years. Seventy-nine per cent of the feet had satisfactory results, and all the failures were due to technical errors of graft placement. The calcaneo-first-metatarsal angle on the standing lateral radiograph was found to be the most objective angle and correlated best with the clinical results. The long term effects on the rest of the foot was negligible, with only 3 of the 10 feet, with a follow-up longer than 12 years showing minimal talonavicular arthritis and only 1 ankle developing a ball and socket joint. Ankle valgus was not a significant problem.

Adolescent

Intraoperative radiation therapy for recurrent head and neck cancer.

Forty-seven patients with recurrent head and neck cancer in a previously irradiated field were treated with surgical resection and intraoperative radiation therapy (IORT). Recurrent disease occurred at a median of 18 months from primary treatment, and was at the primary tumor site in 31 and metastatic to regional lymph nodes in 16. Recurrences were squamous cell carcinomas in 42 and adenoid cystic in five. Surgical resection left microscopic residual disease in 41 and gross residual in six. All patients received IORT with a median of 20 Gy. Two-year actuarial survival is 54.9%, and 15 patients are alive and disease free with a median survival of 29 months. Two-year actuarial local control is 61.5%. A trend toward increased survival (P less than 0.09) and local recurrence control (P = 0.05) was noticed when treating microscopic residual disease as opposed to gross residual disease. Perioperative mortality was seen in 8.5% and there was no increase in morbidity secondary to IORT. The authors believe that surgical resection and IORT is an effective treatment modality for head and neck cancers recurrent in previously irradiated fields and is adaptable to tertiary care hospitals.

Combined Modality Therapy

The complement binding-like domains of the murine homing receptor facilitate lectin activity.

The leukocyte homing receptor (HR), the endothelial leukocyte adhesion molecule, and gmp140/platelet activation-dependent granule membrane protein are members of a family of adhesion molecules, termed the lectin cell adhesion molecules (LEC-CAMS) which are unified by a multi-domain structure containing a lectin motif, an epidermal growth factor-like (egf) motif, and variable numbers of a complement binding-like (CB) motif. Previous data have indicated a predominant role for the lectin motif in cell adhesion directed by the LEC-CAMS, although the egf-like domain of the HR may also play a potential role in cell binding. While the role(s) of the CB domains in the LEC-CAMS is currently not understood, they have been hypothesized to act as rigid spacers or stalks for lectin and perhaps, egf domain presentation. In this paper, we analyze the functional characteristics of murine HR-IgG chimeras containing the lectin, lectin plus egf, and lectin plus egf plus CB domains. The Mel 14 mAb, an adhesion blocking antibody which recognizes a conformational determinant in the N-terminus of the HR lectin domain, shows a significantly decreased affinity for a HR construct which lacks the CB motifs, consistent with the possibility that the CB domains are involved with lectin domain structure. In agreement with this conjecture, HR mutants lacking the CB domains show a profound decrease in lectin-specific interaction with the carbohydrate polyphosphomannan ester, suggesting that the changes in Mel 14 affinity for the lectin domain are reflected in lectin functionality. Various assays investigating the interactions between the HR deletion mutants and the peripheral lymph node high endothelium, including cell blocking, immunohistochemical staining, and radioactively labeled ligand binding, all showed that removal of the CB domains results in a lack of HR adhesive function. These results imply that the CB domains of the HR, and, by analogy, the other members of the LEC-CAM family, may play important structural roles involving induction of lectin domain conformation and resultant functionality.

Antibodies, Monoclonal

Noninvasive optimization of left ventricular filling using esophageal Doppler.

OBJECTIVE: To confirm whether the descending aortic blood flow velocity waveform variable of flow time corrected for heart rate, measured using an esophageal Doppler transducer, can be used for noninvasive optimization of left ventricular (LV) filling. SETTING: ICU and operating theater. SUBJECTS: Forty-three mechanistically ventilated patients in the ICU or undergoing cardiothoracic surgery in whom a pulmonary arterial catheter was in situ. INTERVENTIONS: LV preload was a) increased from hypovolemic states (pulmonary arterial occlusion pressure [PAOP] less than 8 mm Hg) by fluid challenge, b) decreased from normovolemic states (PAOP 10 to 15 mm Hg) by either iv nitrates or intravascular fluid loss, and c) decreased from heart failure or fluid overload states (PAOP greater than 20 mm Hg) by iv nitrates. No other maneuver was performed concurrently. MEASUREMENTS AND MAIN RESULTS: Descending aortic blood flow was measured by an esophageal Doppler transducer. Corrected flow time was calculated by dividing systolic flow time by the square root of the cycle time. PAOP and corrected flow time increased after fluid challenges in hypovolemic states, and decreased when LV preload was decreased from normovolemic states. However, when preload was decreased from overload states, PAOP always decreased, but the corrected flow time usually increased before any subsequent decrease. The greatest value of corrected flow time corresponded with the maximal stroke volume seen. CONCLUSIONS: Esophageal Doppler measurement of aortic blood flow can be used for rapid, noninvasive optimization of LV filling in mechanically ventilated patients.

Aorta

Effects of alterations in left ventricular filling, contractility, and systemic vascular resistance on the ascending aortic blood velocity waveform of normal subjects.

OBJECTIVES: To confirm the consistent effects on Doppler-measured aortic blood flow velocity waveform variables of alterations in left ventricular preload, afterload, and inotropy using pharmacologic and physiologic maneuvers. SETTING: Medical school laboratory. SUBJECTS: Healthy volunteers. INTERVENTIONS: Increasing infusion rates of dobutamine (1.25 to 5 micrograms/kg.min), esmolol (1.25 to 5 mg/min), phentolamine (1.25 to 5 mg/min), methoxamine (1.25 to 5 mg/min), metaraminol (1.25 to 5 mg/min), and placebo (1.25 to 5 mL of 0.9% saline/min) and increasing plasma removal (0.5 to 1 L) in awake, rested, supine subjects. MEASUREMENTS AND MAIN RESULTS: Ascending aortic blood flow was measured by the suprasternal Doppler approach allowing calculation of waveform variables of stroke distance and minute distance (linear measures of stroke volume and cardiac output), peak velocity, mean acceleration and flow time corrected for heart rate. An index of systemic vascular resistance was obtained by dividing mean systemic BP by the minute distance. Inotropic changes predominantly affected peak velocity and mean acceleration. Changes in preload mainly affected the flow time corrected for heart rate, whereas afterload changes had an intermediate effect. Unsuspected but subsequently confirmed hemodynamic effects were seen with esmolol and metaraminol. CONCLUSIONS: Aortic blood flow velocity waveform variables measured by Doppler ultrasound can be used to noninvasively follow changes in left ventricular preload, afterload, and inotropy.

Adrenergic beta-Antagonists

Haemodynamic evidence for per-operative cardiac stress during transurethral prostatectomy. Preliminary communication.

Haemodynamic changes were measured during routine transurethral prostatectomy (TURP). The heart rate and stroke volume fell progressively over the first 30 min of surgery, resulting in a steady reduction in cardiac output. There was a significant increase in left ventricular afterload from commencement of the procedure. These findings demonstrate that haemodynamic responses, which are not detectable using conventional methods of monitoring, occur during TURP. Increased left ventricular afterload indicates increased myocardial work and oxygen demand which could result in myocardial ischaemia. This may contribute to the increased cardiovascular morbidity and mortality which have been reported to occur after TURP. The possible underlying mechanisms are discussed.

Aged

The Escherichia coli ts8 mutation is an allele of fda, the gene encoding fructose-1,6-diphosphate aldolase.

The ts8 mutant of Escherichia coli has previously been shown to preferentially inhibit stable RNA synthesis when shifted to the nonpermissive temperature. We demonstrate in this report that the ts8 mutation is an allele of fda, the gene that encodes the glycolytic enzyme fructose-1,6-diphosphate aldolase. We show that ts8 and a second fda mutation, h8, isolated and characterized by A. Böck and F. C. Neidhardt, are dominant mutations and that they encode a thermolabile aldolase activity.

Alleles

Physiological effects of the fructose-1,6-diphosphate aldolase ts8 mutation on stable RNA synthesis in Escherichia coli.

The conditional lethal mutations ts8 and h8 are located in fda, the gene encoding aldolase, and they inhibit RNA synthesis upon shift to the nonpermissive temperature. We demonstrate that both mutations preferentially inhibit stable RNA synthesis and that this inhibition occurs at the level of transcription initiation. The susceptibility of a promoter to the inhibitory effects of ts8 is correlated with the ability of the promoter to be growth rate regulated. This effect is independent of relA and spoT function. Inhibition is dependent upon glucose metabolism past the generation of glucose-6-phosphate; however, the mechanism of this effect is unknown.

Escherichia coli