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Biomedical subjects

M Meyers

Publications and source records attributed to M Meyers.

At least 55 records · Page 3Linked to original sources

The differential hemispheric processing of emotion: a comparative analysis in strongly-lateralized sinistrals and dextrals.

The neural processing of emotion and the differential processing of affect and cognition are thus far poorly understood. Complex results across studies suggest involvement of the left hemisphere, the right hemisphere, or both. Since handedness is related to cerebral dominance, the present study undertook a comparative analysis of neural processing in strongly lateralized left- and right-handed populations. Parietal EEG and bilateral electrodermal activity were recorded while carefully selected subjects were exposed to emotional stimuli under cognitive, affective, and neutral conditions. Results showed greater lateral differentiation and differentially greater left-hemisphere activation in dextrals but greater overall activation in sinistrals. These findings are consistent with the common observation that cerebral organization is more diffuse in left-handed populations. It seems clear that the comparative study of sinistrals and dextrals can help us to better understand how emotion is processed in the brain.

Brain↗

Antimelanoma monoclonal antibody-ricin A chain immunoconjugate (XMMME-001-RTA) plus cyclophosphamide in the treatment of metastatic malignant melanoma: results of a phase II trial.

Prior studies with the XMMME-001-RTA immunoconjugate composed of an antimelanoma monoclonal antibody and ricin A chain demonstrated some antitumor activity. However, almost all patients studied developed human antimurine antibodies and antiricin antibodies. In an effort to abrogate these host anti-immunotoxin immune responses and thus enhance antitumor activity, we treated 20 patients with the immunoconjugate plus a single dose of intravenous cyclophosphamide. An overall response rate of 20% was observed-predominantly in pulmonary and soft tissue nodules. There was no diminution in antibody responses against either the murine antibody or the ricin moiety. Further studies to elucidate the role of cyclophosphamide in monoclonal antibody therapy are planned.

Adult↗

Histological and biomechanical assessment of articular cartilage from stored osteochondral shell allografts.

Normal and stored articular cartilage from the medial tibial plateaus of mature canine knee joints were evaluated histologically and biomechanically. The medial plateaus from the right knee (control) were assessed fresh, while the left (stored) were preserved in culture media at 4 degrees C for 3, 7, 14, or 28 days and then evaluated. Biomechanically, confined compression tests were performed on all specimens to determine the aggregate modulus and apparent permeability of the articular cartilage. Histologically, Safranin O- and hematoxylin and eosin (H&E)-stained sections were evaluated. All stored cartilage specimens had an aggregate modulus on average lower than normal, but the differences were not significant (p greater than 0.10). The apparent permeability was on average higher than but also not significantly different from normal (p greater than 0.10). Time in storage (up to 28 days) did not have a significant effect on the biomechanical properties of stored cartilage normalized by control values (p greater than 0.50). Safranin O and H&E histological evaluation also showed no overall changes in cell appearance or staining of the stored cartilage when compared with control for the time periods studied.

Animals↗

Phase II study of carboplatin in recurrent ovarian cancer: severe hematologic toxicity in previously treated patients.

Carboplatin (CBDCA) is a second-generation cisplatin analog that has shown activity in early clinical trials. Its spectrum of toxicity is quantitatively and qualitatively different from that of the parent compound. Between November 1984 and September 1986 we conducted a phase II trial of CBDCA in 46 women with epithelial ovarian cancer. All patients had undergone at least one prior chemotherapy regimen; 41 (89%) had previously received cisplatin (mean cumulative dose, 540 mg/m2). The CBDCA dose was based on renal function and was injected i.v. once every 4 weeks. Patients were stratified on the basis of baseline creatinine clearance: those with a baseline creatinine clearance of greater than or equal to 60 ml/min received 400 mg/m2 CBDCA; those with a creatinine clearance between 30 and 60 ml/min received an initial dose calculated according to a previously published formula that corrected for renal insufficiency and projected nadir platelet counts of 75,000/mm3. Of 41 evaluable patients, 6 (15%) had an objective response [2 complete responses (CRs); 4 partial responses (PRs)]; 5 of the 6 responders had previously responded to cisplatin treatment. No responses were observed in 12 patients who had not responded to prior cisplatin therapy. Significant hematologic toxicity was seen. Of 18 patients with a creatinine clearance of greater than or equal to 60 ml/min (dose, 400 mg/m2), 6 had nadir platelet counts of less than 25,000/mm3, 4 with symptomatic bleeding. Of the 21 evaluable patients for whom the dose-modification formula was applied, 10 had nadir platelet counts of less than 75,000/mm3; 5 had counts of less than 50,000/mm3. CBDCA has activity even in patients who have previously undergone extensive cisplatin therapy; however, its toxicity is variable and thrombocytopenia is dose-limiting. We did not confirm the ability of the above-mentioned formula to calculate the CBDCA dose and accurately predict the nadir platelet count for all patients. Other factors, such as prior radiotherapy, may also be important in the dosing of CBDCA in pretreated patients.

Acute Disease↗

Parietal processing of affect and cognition: cerebral organization in strongly lateralized left-handed subjects.

Cerebral organization for the processing of emotion and for the differential processing of affect and cognition have thus far been studied exclusively in right-handed subjects. Since handedness is related to cerebral dominance, our understanding of the neural processing of affect and cognition should be further enhanced by the study of sinistral subjects. The present study examined the differential parietal processing of emotional stimuli under affective and cognitive conditions in left-handed subjects. The subjects were exposed to emotional stimuli presented under affective and cognitive instructional sets and to neutral, control stimuli. Bilateral electroencephalographic and bilateral electrodermal activity data showed greater responsiveness to emotional than neutral stimuli but no differential lateralization of affect and cognition in left-handed subjects. Results also showed that female subjects were more responsive to emotional stimuli than male subjects. Results were interpreted as suggesting that left-handed individuals may be less strongly lateralized for the differential processing of affect and cognition than right-handed individuals and that females may have greater focal organization for the processing of emotion than males.

Adult↗

A histological and biochemical assessment of the cartilage matrix obtained from in vitro storage of osteochondral allografts.

Fresh osteochondral allografts were stored at 4 degrees C in tissue culture media at variable time periods (3, 7, 14 and 28 days). Sterilely dissected tibial plateaus with a standardized 1/2 cm subchondral bone "shell" were obtained from canines 1-3 hrs post mortem. X-rays were taken to determine maturity of the animals. Only mature animals (closed epiphyses) were considered for the study. Histologically, safranin 0 (metachromatic stain for glycosaminoglycans) was observed in all experimental specimens. H&E stained sections showed at all time periods of 3, 7, 14 and 28 days that the cell morphology and arrangements were similar in the superficial and deep areas of the cartilage obtained from the stored osteochondral allograft when compared to the control articular cartilage. The cells were in lacunae and arranged in clusters. Biochemically, glycosaminoglycans and collagen content showed no difference at the 95% level of confidence during the duration of the study (28 days) when compared to the 0 day control cartilage. Collagen typing, based on the assessment by HPLC of the CNBr peptides showed the major presence of type II collagen (no evidence of dedifferentiation was observed). No type I was found to be present. Some apparent variations in the proportions of minor collagen components were noted--e.g. at 14 days the cartilage appeared to contain increased amounts of type XI but little or no type IX collagen (HMW, LMW) when compared to the day 0 control. At 28 days a shift to a larger amount of type IX collagen occurs, especially in the LMW component, with a small amount of type XI collagen when compared to normal day 0 articular cartilage. Cell viability, i.e., the ability of the allograft tissue to incorporate 35SO4 in the synthesis of glycosaminoglycans, was intact up to 28 days of storage.

Animals↗

Phase I study of the combination of alpha-2 interferon and cisplatinum.

Based on preclinical evidence of synergy, we performed a Phase I study of the combination of alpha-2 interferon and cisplatinum in patients with advanced malignancy. A fixed dose of 5 x 10(6) U/m2 alpha interferon was given three times weekly. Cisplatinum was given once weekly at dose levels of 5, 10, 20, 25, and 30 mg/m2. Dose-limiting toxicity consisted of flu-like symptoms and malaise leading to decreased performance status. Response was seen in a patient with metastatic melanoma. Recommended doses for Phase II study are 5 x 10(6) U/m2 of alpha-2 interferon three times weekly and 25 mg/m2 of cisplatinum once weekly.

Cisplatin↗

Computed tomography with multiplanar reformation and three-dimensional image reconstruction in the preoperative evaluation of adult hip disease.

Computed tomography (CT) with multiplanar reformation and three-dimensional (3D) image reconstruction was used pre-operatively to outline the bony morphological changes and femoral-acetabular relationships in 25 adult patients suffering from hip disease. Diagnoses included ischaemic necrosis of the femoral head, osteoarthritis, rheumatoid arthritis, calcium pyrophosphate dihydrate (CPPD) crystal deposition disease, previous trauma and chronic dislocation. Polyethylene models of the femora and acetabula were constructed from three-dimensional contouring of CT data and compared with resected specimens in patients subjected to subsequent total hip arthroplasty. Information provided by this imaging technique was useful in both selecting and guiding the most appropriate surgical procedure and it was found that models depicted the actual bony contours with reasonable accuracy. CT combined with multiplanar reformation and 3D analysis may be the optimal pre-operative means of assessment of the diseased adult hip.

Acetabulum↗

Hemispheric asymmetry and emotion: lateralized parietal processing of affect and cognition.

The differential cerebral processing of affect and cognition may have important implications for a more general understanding of how these two complex sets of functions differ and how they interact. Building upon recent studies of hemispheric asymmetry in emotion, the present study focused on the differential parietal processing of emotional stimuli under affective and cognitive conditions. Subjects were exposed to neutral and emotional stimuli presented under cognitive and affective instructional sets. Bilateral electroencephalographic (EEG) data showed that the principal differentiation between affective and cognitive conditions occurred in the right hemisphere, whereas the highest overall level of activation during emotional stimulation was in the left hemisphere. It was also found that affective conditions produced higher of levels of both EEG and electrodermal activity than either cognitive or neutral conditions. Finally, significant patterns of gender differentiation suggested greater focal organization for affective arousal in females than males.

Affect↗

Hemispheric asymmetry and emotion: effects of nonverbal affective stimuli.

The purpose of the present study was to investigate the cerebral processing of affect by measuring the electroencephalographic activity of the frontal lobes and electrodermal activity in response to a series of nonverbal affective stimuli. Cognitive and sensorimotor processes were minimized by employing a design that did not require subjects to perform any task other than attending to the stimuli. Summated frontal alpha activity was determined during nonemotional, positive, and negative stimuli. Changes in bilateral skin conductance were also measured during the presentation of the stimuli. Results demonstrated that there was bilateral activation of the frontal lobes in response to the positive affective stimuli. The level of activation of the frontal lobes was the same in response to both negative and nonemotional stimuli. There was no evidence of hemispheric asymmetry or gender-related differences in patterns of activation. Furthermore, there was no evidence of lateralization in the skin conductance response magnitude.

Acoustic Stimulation↗

A technique for multiplanar reformation and three-dimensional analysis of computed tomographic data: application to adult hip disease.

A commercially available system which is able to accept input from computed tomographic (CT) or magnetic resonance (MR) scanners was used preoperatively to generate multiplanar reformations (MPR) and three-dimensional (3D) images depicting the osseous morphologic alterations and femoral-acetabular relationships in 25 adult patients with a variety of hip diseases. Polyethylene surface representations of femora and acetabulae were constructed by the 3D-contouring of CT data and were then compared to resected specimens from patients who subsequently underwent total hip arthroplasty. Information provided by this imaging strategy was useful in both selecting and guiding the most appropriate surgical procedure, and the models depicted actual osseous contours with reasonable accuracy. The system employed has distinct advantages over other previously described 3D imaging strategies, which include a menu-driven user-friendly interface, data base access via reference images, 3D sectional analysis, and contour file editing for selective visualization of desired structures.

Acetabulum↗

Computed tomography with multiplanar reformation and 3-dimensional image analysis in the preoperative evaluation of ischemic necrosis of the femoral head.

Computed tomography (CT) with multiplanar reformation and 3-dimensional image reconstruction were utilized preoperatively to assess the extent of infarction and collapse of the femoral head in 15 patients with ischemic necrosis. Polyethylene models of the diseased femoral heads were constructed from 3-dimensional contouring of CT data, and compared with resected specimens in patients who underwent subsequent total hip arthroplasty. Information provided by this imaging strategy was valuable in both the selection and the planning of the most appropriate surgical procedure, and models were found to represent resected head configurations with reasonable accuracy. CT combined with multiplanar reformation and 3-dimensional analysis may be the optimal preoperative means for evaluating advanced ischemic necrosis involving the femoral head.

Adult↗

Fetal tachycardia and intramyocardial tumors.

The two-dimensional echocardiographic diagnosis of multiple cardiac rhabdomyomas and evaluation of tachycardia in a fetus are presented. Prenatal echocardiographic examination defined the extent of tumor involvement and mechanism of the tachycardia and demonstrated the lack of fetal hemodynamic compromise. Perinatal, clinical and therapeutic implications are discussed.

Adult↗

Sodium nitroprusside for control of severe hypertensive disease of pregnancy: a case report and discussion of potential toxicity.

Sodium nitroprusside has been used to alter blood pressure in severe hypertensive disease of pregnancy; however, concern exists in regard to potential lethal complications from cyanide toxicity in both mother and fetus. We recently evaluated levels of cyanide in the liver of an infant stillborn to a woman in whom sodium nitroprusside was used to control gestational hypertension secondary to mitral valve disease. The fetal liver demonstrated levels of cyanide below toxic ranges. Biologic activity, potential toxicity, and treatment of toxic symptoms of nitroprusside are discussed.

Adult↗

Steroid D-ring glucuronides: characterization of a new class of cholestatic agents.

In summary, we have shown that steroid D-ring, but not steroid A-ring, glucuronide conjugates act at the level of the bile canaliculus to decrease bile-acid-dependent flow, initially; and subsequently, bile-acid-independent flow. These data indicate that glucuronide conjugates are not necessarily inactive; the present glucuronides clearly possess toxicological activity. The cholestatic glucuronides are all natural, endogenously formed products of metabolism. The critical questions which remain are whether metabolism of steroids to D-ring glucuronides is an obligatory step in the etiology of steroid-induced cholestasis and whether these glucuronides, at concentrations attained in humans, are capable of decreasing hepatic excretory function and inducing morphological and biochemical changes of clinical importance.

Animals↗

Hepatotoxic effects of estradiol-17 beta-D-glucuronide in the rat and monkey.

The steroid D-ring glucuronide conjugate estradiol-17 beta-D-glucuronide (E217G) but not the A-ring conjugate E23-glucuronide (E23G) has been shown to inhibit bile flow in the rat. To determine if primates are also sensitive to E217G-induced cholestasis, a noninvasive approach with the use of indocyanine green (ICG), a dye eliminated primarily by biliary excretion, was first validated in the rat and then applied to the rhesus monkey. ICG (16 mg/kg rat; 4 mg/kg monkey) was administered i.v. 10 min after an i.v. bolus dose of either E217G (5.5 or 11 mumol/kg), E23G (11 mumol/kg) or vehicle alone. In the rat, the elimination T1/2 of ICG was increased by the 11 mumol/kg dose of E217G (P less than .025), whereas E23G produced no significant change from vehicle control values. In the monkey, the 5.5 and 11 mumol/kg doses of E217G increased the T1/2 of ICG in a dose-related manner (P less than .005), whereas E23G was without effect. Plasma levels of total radioactivity demonstrated dose-dependent kinetics after the administration of a tracer dose and 11 mumol/kg of [3H]E217G. A rebound of plasma radioactivity was seen at 11 mumol/kg of [3H] E217G, the time course of which mimicked the time course of E217G-induced cholestasis. High-performance liquid chromatographic analysis of rat bile and plasma after the administration of [3H]E217G revealed primarily E217G and estradiol-3-sulfate-17 beta-D-glucuronide together with small amounts of three unidentified metabolites. In the monkey, only E217G and estradiol-3-sulfate-17 beta-D-glucuronide were observed in the plasma after the administration of [3H]E217G. In contrast to E217G, estradiol-3-sulfate-17 beta-D-glucuronide was choleretic in the bile duct-cannulated rat model. These data indicate that E217G is hepatotoxic in both rodents and nonhuman primates.

Animals↗