Biomedical subjects
G S Weinstein
Publications and source records attributed to G S Weinstein.
Intent-to-treat analysis.
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Isocratic high-performance liquid chromatography-photodiode-array detection method for determination of lysine- and arginine-vasopressins and oxytocin in biological samples.
A simple, isocratic, sensitive (1 ng), and specific high-performance liquid chromatographic (HPLC) method based on photodiode-array detection (PAD) is described for simultaneous quantitation of the bioactive peptides, lysine vasopressin (LVP), arginine vasopressin (AVP) and oxytocin (OXY). Acidified pig plasma and left ventricular (LV) tissue samples were first extracted with Sep-Pak C18 columns, and the bioactive peptides were eluted with methanol, then dried at 37 degrees C and reconstituted with HPLC mobile phase. The bioactive peptides were separated by HPLC on a Dynamax 3009-A C8 column with a mobile phase of 0.1% trichloroacetic acid-50 mM heptanesulfonic acid-30mM triethylamine-20% acetonitrile in water, pH 2.5 and identified with a Waters 990-PAD system (spectrum index plots in the range 200-400 nm). Standards of LVP, AVP and OXY and their mixtures showed a linear increase in the range 5 to 100 ng and were eluted at 6.1, 6.9 and 4.6 min, respectively. Spectrum analysis showed a distinct absorption peak at 280 nm, corresponding to peptide bonds. The reproducibility of the method coefficient of variation for standards is 6.9, 5.8 and 4.7% for LVP, AVP and OXY, respectively. In plasma and tissue it is much higher: 12.9% (LV tissue) and 18.6% (plasma) for LVP. Pig plasma contains negligible amounts of AVP and OXY; LVP is much higher (0.28 +/- 0.19 ng/ml). In pig tissue, LVP predominates (6.95 ng/g wet weight) compared to AVP (1.45) and OXY (1.50). Spectral analysis is necessary to identify the bioactive peptide peaks among interfering substances and to increase the sensitivity four-fold. The method described here is useful for the simultaneous determination of LVP, AVP and OXY in the nanogram range and can be extended to picogram levels by employing PAD spectral analysis techniques.
Protection of ischemic heart from reperfusion injury by myo-inositol hexaphosphate, a natural antioxidant.
Myo-inositol hexaphosphate (phytic acid), a highly charged antioxidant, has been found to chelate metal ions such as iron and calcium and to scavenge hydroxyl radicals, .OH. This study examined the efficacy of this antioxidant and redox agent in attenuating myocardial reperfusion injury. Sprague-Dawley rats were injected intravenously with three different doses of phytic acid (group 1, saline solution only, control; group 2, 1.5 mg/100 g; group 3, 7.5 mg/100 g; group 4, 15 mg/100 g) 30 minutes before excision of hearts. Isolated hearts were prepared by the Langendorff technique. Global ischemia was induced for 30 minutes, followed by 30 minutes of reperfusion. As expected, in group 1, reperfusion was associated with enhanced creatine kinase release, reduced coronary flow, poor recovery of ventricular function as evidenced by reduced left ventricular developed pressure and the first derivative of left ventricular pressure, and increased lipid peroxidation. Groups 3 and 4, but not group 2, demonstrated myocardial protection as evidenced by reduced creatine kinase release, improved left ventricular function and coronary flow, and decreased lipid peroxidation compared with the control group. These results suggest that potential use of this antioxidant in salvaging the heart from ischemic and reperfusion injury.
Crossovers in coronary artery bypass grafting trials.
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Reduction of myocardial injury with verapamil before aortic cross-clamping.
The effect of verapamil administered before aortic cross-clamping was assessed in 40 patients undergoing elective coronary artery bypass grafting. Myocardial protection consisted of cold blood potassium cardioplegia, topical ice slush, and moderate (28 degrees C) systemic hypothermia. Patients were randomly divided into two groups: group 1 (18 patients) received verapamil (0.1 mg/kg up to 10 mg) intravenously three to five minutes before aortic cross-clamping; group 2 (22 patients) did not (control). Myocardial injury was assessed by cumulative release of the cardiac-specific isoenzyme of creatine kinase (CK-MB) after release of the aortic cross-clamp. Release of CK-MB was significantly lower in the verapamil group (44.9 +/- 6.2 versus 72.2 +/- 9.0 IU at 24.5 hours, p = 0.005). Calculated total infarct size was also lower in the verapamil group (6.0 +/- 0.9 versus 8.9 +/- 1.0 g-Eq, p = 0.035). Individual CK-MB release curves showed either one or two peaks. The two-peak pattern was more frequent in control patients (18 of 21 control patients versus 6 of 18 verapamil patients, p = 0.001) and was associated with a larger infarct size. Atrioventricular pacing was not required in any verapamil patient, but was needed in 1 control patient. We conclude that verapamil administered before aortic cross-clamping protects against myocardial injury during coronary artery bypass grafting with no increase in the incidence of atrioventricular block.
Anomaly of the hypoglossal nerve: embryologic, anatomic, and surgical considerations.
An anomaly of the hypoglossal nerve was discovered during a procedure to anastomose the 12th and 7th cranial nerves. This anomaly is described, and an embryologic mechanism is proposed to explain the occurrence of this particular anomaly. The surgical anatomy of the hypoglossal nerve is reviewed, and reasonable approaches to the surgical identification of the hypoglossal nerve are discussed.
Effect of oxygen free radicals and lipid peroxides on cardiac isoenzymes.
We report here the effect of oxygen free radicals, OFR (superoxide, O2-; hydroxy, OH; t-butylhydroperoxide, H2O2) lipid peroxides (malondialdehyde, MDA), free radical scavengers (superoxide dismutase, catalase, allopurinol) and generator (ferrous chloride) antioxidants (ascorbate, glutathione) spin traps (5,5-dimethyl-1-pyroline-N-oxide, N-t-butyl-L-pheny nitrone) on the cardiac isoenzyme (CK, CK-MB, LDH, LD1) concentrations in the sera of patients with acute myocardial infarction. CK-MB and LD1 were rapidly and completely inactivated by O2- (50 nmol/ml), OH (1 nmol/ml) and MDA (0.6 microM). Butylhydroperoxide (600 microM), and ferrous chloride (200 microM) selectively inhibited CK-MB. The free radical scavengers, antioxidants and spin traps all had minimal effects, and H2O2 had none.
Serial changes in renal function in cardiac surgical patients.
Cardiopulmonary bypass is widely believed to be injurious to renal function. The low incidence of renal dysfunction with modern techniques of bypass led us to reexamine this concept by monitoring urine output and creatinine clearance in 18 adult patients undergoing nonpulsatile, hemodilution cardiopulmonary bypass for coronary artery bypass grafting (12 patients) or valve procedures (6 patients). Samples were taken before, during (mean duration of bypass, 105 +/- 26 minutes [+/- standard deviation]), and every two hours after bypass for 24 hours. Urine output (42 +/- 37.7 mL/h) and creatinine clearance (57 +/- 40.4 mL/min) were surprisingly low in the period before cardiopulmonary bypass (all values normalized to a body surface area of 1.73 m2). Urine volumes rose to 305 +/- 149.6 mL/h and creatinine clearance to 252 +/- 176.9 mL/min during bypass and decreased to stable values after eight hours in the postoperative unit (urine output, approximately 60 mL/h, and creatinine clearance, approximately 75 mL/min). Renal dysfunction did not develop in any patient. Nine patients who required loop diuretics for low urine output 18 hours postoperatively had a sustained increase in both urine output and creatinine clearance lasting up to six hours. We conclude the following: modern techniques of cardiopulmonary bypass are not injurious to renal function; urine output and creatinine clearance are decreased before cardiopulmonary bypass, probably because of preoperative dehydration; and loop diuretics in the postoperative period increase both urine output and creatinine clearance for as long as six hours after administration.
Effect of crossover on the statistical power of randomized studies.
Randomized studies involving long-term follow-up are vulnerable to the effects of unplanned crossover. In surgical studies, such crossover usually occurs when control patients become more symptomatic and undergo operation. In several large studies of coronary bypass grafting, crossover ranged from 25% to 38%. The most common way of dealing with this problem is to apply the "intention-to-treat" principle, which analyzes such crossovers with their originally assigned groups. Besides the logical problem of counting a control patient who actually undergoes operation as "nonsurgical," a more subtle problem arises in terms of statistical power. When statistical power is low, a truly effective treatment may be mistakenly labeled as no better than control, causing a potentially valuable form of therapy to be ignored or discarded. This analysis demonstrates that crossover may have a profound effect on the statistical power of randomized studies and presents a method for predicting the effect of such crossover on statistical power.
Single-source outbreak of Candida tropicalis complicating coronary bypass surgery.
Candida tropicalis was isolated from the sternal wounds of eight coronary bypass patients from 18 to 89 days postoperatively; infections were limited to soft tissue in five patients but involved the sternum in three patients. Analysis of surgery records implicated one individual as the potential source of the yeast; this was confirmed by microbiological studies of fingertips and nasopharynx cultures of all personnel in contact with these patients. Only the suspect nurse, then acting as a scrub nurse and not as a circulator, infected the eight patients. Her removal from the cardiac team terminated the cluster outbreak.
Adenoid cystic carcinoma of the parotid gland: a review of surgical management with reference to the facial nerve.
The purpose of this study was to review a large series of patients with adenoid cystic carcinoma of the parotid gland in order to develop clinical criteria for sacrifice versus selective sparing of the seventh nerve. We studied 43 patients followed over 36 years. Study patients were grouped according to the preoperative status and intraoperative management of the facial nerve. Criteria for choosing various management strategies are discussed.
Deferoxamine decreases necrosis in dorsally based pig skin flaps.
Deferoxamine, a free radical scavenger and iron chelator, has been shown to improve skin flap survival in ischemic flap surgery in rats. The present study investigates the value of deferoxamine in ischemic flap surgery in the porcine model. Four 4 x 12 cm flaps, 3 cm apart and 3 cm from the dorsal midline, were elevated on each of six female pigs, weighing 50 to 60 pounds each. The animals were divided into two test groups. Group 1 received six 1 gm doses of deferoxamine in 4 ml of sterile water intramuscularly every 6 hours preoperatively for five doses, followed by the administration of 1 g every 6 hours for the first 6 days postoperatively. Group 2 received 4 ml of normal saline administered intramuscularly as above. The percentage of flap necrosis was assessed on postoperative day 7 by the weighing paper technique. Group 1 had 17.1% necrosis and group 2 had 33% necrosis (p less than 0.005). Deferoxamine has decreased flap necrosis in the porcine model and may be of use in augmenting the surviving length of flaps in human beings.
Identification of the levator aponeurosis in the correction of eyelid ptosis.
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Lower eyelid reconstruction with tarsal flaps and grafts.
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Full-thickness bipedicle flap for total lower eyelid reconstruction.
We describe a technique for total lower eyelid reconstruction utilizing a full-thickness bipedicle flap from the upper eyelid. The levator aponeurosis and Müller's muscle are recessed to avoid upper eyelid retraction. The key to performing this operation is a thorough knowledge of eyelid anatomy and techniques for preserving its microvascular blood supply. The bipedicle flap requires meticulous surgical technique but has many advantages over standard types of total lower eyelid reconstruction, including the following: excellent tissue match and cosmesis are obtained with single-stage reconstruction; distal flaps and grafts are avoided; open palpebral fissure is maintained, resulting in rapid rehabilitation; posterior lamella of tarsus, rather than substitute, is utilized; anterior lamella of functional orbicularis is utilized for support and closure; pedicles suspend and support the eyelid, decreasing lower eyelid retraction, laxity, and ectropion; allows simultaneous reconstruction of canthal defects; and is faster than other forms of total lower eyelid reconstruction. The results of 14 total lower eyelid reconstructions are presented. Minor canthal deformities, the most frequent complication, are easily corrected. This technique should be considered as an alternative to other procedures in cases of total lower eyelid reconstruction.
Use of a dental mirror for postoperative eyelid examination.
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