Biomedical subjects
Publications and source records attributed to L Glantz.
We report a case of akathisia developed after administration of 2.5 mg metoclopramide for treatment of nausea during cesarean section. The relevant literature as well as options for prevention and treatment of this phenomenon are reviewed.
Patients having cataract surgery are usually elderly and have risk factors for ischemic heart disease. We sought to determine the incidence of perioperative myocardial ischemia in patients having cataract surgery and compare the influence of local anesthesia (LA) and general anesthesia (GA). Eighty-one patients undergoing cataract surgery with at least two risk factors for ischemic heart disease were monitored continuously for 24 h by using electrocardiogram leads II and V5 and a Holter recorder (Medilog 4500, Oxford Ltd, UK). Patients were randomly allocated to two groups, either LA (n = 39) or GA (n = 42). In the LA group, a peribulbar block was performed, whereas a similar block was performed in the GA group after tracheal intubation. The study demonstrated that cataract patients suffered from a frequent incidence of perioperative myocardial ischemia (31%). There was no difference in the incidence rate between the groups: 12 of 39 in the LA group and 13 of 42 in the GA group (P: = NS). However, the number of ischemic episodes was significantly increased in the GA group (18 vs. 13 in the LA group) (P<0.05), and there were significantly more intraoperatively in the GA group (8 vs. 1) (P<0.01). All intraoperative ischemic events were associated with tachycardia (> or =20% of baseline), whereas postoperative ischemic changes were mostly independent of heart rate. Only one of the ischemic patients (in the GA group) was admitted as a result of intractable chest pain. There were significantly less intraoperative episodes in the LA group, suggesting that LA may be safer than GA in patients during this type of surgery.
OBJECTIVE: Intracerebral hemorrhage (ICH) is associated with a high mortality. The present study sought to determine the incidence of spontaneous ICH in an intensive care unit (ICU) and associated factors. DESIGN: A 6 year retrospective study. SETTING: A general ICU in a university hospital. PATIENTS: All ICU patients developing ICH were included in the study. All trauma and neurosurgical patients were excluded, as well as patients who were admitted to the ICU because of ICH. MEASUREMENTS AND RESULTS: During the study period 3032 patients were hospitalized in the ICU, and 834 were excluded. The remaining 2198 patients comprised the study population. Computed tomography of the head was performed in a total of 227 patients, and the 9 patients found to have new onset ICH comprise the group of interest. None of these patients were hypertensive. Seven of the patients had either a primary hematologic malignancy or bone marrow transplantation. Eight had thrombocytopenia of <100x10(9)/l (median 10x10(9)/l, range 3-150x10(9)/l), and in 6 it preceded ICH by 5 days or more. Only in one patient were both PTT and PT prolonged. All were mechanically ventilated with high peak inspiratory pressure (PIP) (median 37 cm H2O, range 20-43 cm H2O). Arterial carbon dioxide tension (PaCO2) was considerably elevated (median 65 mm Hg, range 41-87 mm Hg). All of the patients had impaired renal and hepatic function (urea: median 14 mmol/l, range 9.9-52 mmol/l; bilirubin: median 94 micromol/l, range 20-360 micromol/l), and five had septicemia. Eight of the patients bled to other sites before they developed ICH. All patients died shortly after the diagnosis of ICH. CONCLUSIONS: Spontaneous nonhypertensive ICH is a rare, fatal event in the ICU. Associated factors include thrombocytopenia, the need for mechanical ventilation, elevated PIP and PaCO2, sepsis, and impaired hepatic and renal function.
BACKGROUND: Age, illness severity, functional status, and education are associated with advance directive completion. We examined these patient characteristics and discussions with attorneys and physicians in a predictive model for advance directive completion. METHODS: We did a cross-sectional survey of 255 randomly selected patients in a VA outpatient clinic. RESULTS: Patients were predominantly men (95.2%), married (61.9%), with a mean age of 63.2 years; 17.7% of the patients had an advance directive; 5.0% had only a living will, 6.0% had only a durable power of attorney for health care, and 6.7% had both. Age, marital status, illness severity, previous serious illness in spouse, and physician discussion were all associated with advance directive completion in a multiple logistic regression. Eighty-two patients were asked about discussions with attorneys--15 had advance directives; of these, 13 had talked to an attorney, but only 7 had talked to a physician. CONCLUSIONS: Previous serious spousal illness, marital status, age, illness severity, and patient-physician discussions all predicted completions of an advance directive. Attorney discussions were strongly associated with advance directive completion. Better communication between physicians, patients, and attorneys may increase the usefulness of advance directives.
A 63-year-old woman with metastatic breast cancer was referred to our bronchoscopy unit for outpatient laser resection of an endobronchial mass through fiberoptic bronchoscopy. The patient had no history of ischemic heart disease. During the procedure, the patient developed an ST-segment elevation and a complete atrioventricular block. IV nitroglycerin and morphine were effective in treating this episode. In this patient, we were able to demonstrate a focal spasm by postbronchoscopy coronary angiography.
Chondrosarcomas are alleged to be resistant to chemotherapy. A retrospective review of our experience primarily with dedifferentiated chondrosarcomas treated with chemotherapy was performed to reevaluate the efficacy of chemotherapy for this tumor. There were 18 patients: 14 stage IIB and four stage III. Seventeen patients had dedifferentiated chondrosarcoma. The median age at diagnosis was 57 years. Fourteen of the patients underwent wide excision of the tumor, two underwent amputation, and two had no surgery. The femur and the pelvis were the most common locations of the primary tumor. Chemotherapy for 11 of the patients consisted of cisplatin and doxorubicin. Survival was analyzed with the Kaplan-Meier method; the median survival was 12 months. The hypothesis that chondrosarcomas express P-glycoprotein was tested. Expression of P-glycoprotein was evaluated by immunostaining with use of the C494 and C219 antibodies on 41 benign and malignant cartilage tumors, six of which were from the patients in the chemotherapy group. Immunostaining revealed that 37 of 41 cartilage tumors expressed P-glycoprotein. The rate of survival of patients with high-grade chondrosarcoma treated with chemotherapy is poor. P-glycoprotein expression is common in benign and malignant cartilage lesions. The lack of response to chemotherapy may be related to the expression of P-glycoprotein.
The new anticancer agent Taxol appears to potentiate the effects of radiation on brain tumor cell lines in vitro and was recently evaluated by our group as a radiosensitizer in a phase I study for primary brain tumors. In that study, we administered Taxol as a three-hour IV infusion repeated every week for six weeks and gave daily cranial irradiation concurrently for a total of 6000 rads. We reviewed the charts of the 60 patients who participated in the study, and identified twelve patients who underwent a second surgery after treatment because of progressive symptoms and an enlarging intracranial mass on MRI. Pathologically, each patient showed prominent radionecrosis, and other evidence of accelerated radiation changes (confluent areas of coagulative necrosis, bizarre nuclei, marked thickening and fibrinoid changes in multiple blood vessels). These changes were noted many weeks earlier than would be expected after radiation therapy alone and were independent of age, and tumor histology. We postulate that the accelerated radiation changes may be due to the radiation sensitizing effects of Taxol. We also noted a change of the pattern of tumor recurrence, compared to historic reports, and a dose-necrosis relationship where the resected tumor is formed completely of necrotic tissue in patients who received 150 mg/m2 or higher dose of Taxol. These observations may be of significance for future study design.
To individually tailor chemotherapy for patients with malignant gliomas according to tumor chemosensitivity, a rapid assay system which can be performed with a high success rate is needed. The fluorescent cytoprint assay (FCA) can assess multiple chemotherapeutic agents using small (approximately 500 cells) tumor aggregates very quickly (approximately 1 wk). Tissue samples from 51 patients with malignant gliomas obtained either at time of initial diagnosis (n = 34) or at recurrence were assayed using this method. The assay success rate approached 90% in those culture samples which were histologically verified as tumor. A meaningful number of agents could be tested both on samples obtained by stereotactic biopsy (median, 5) and on specimens from more extensive resections (median, 6). One hundred ninety-three FCAs were performed on a samples obtained from 36 patients. In only twenty six assays (14%) was an agent deemed sensitive (> 90% cell kill) to a chemotherapeutic agent. Sixty-two percent of sensitive FCAs were observed in tumors tested against the activated analog of cyclophosphamide, 4-hydroxyperoxycyclophosphamide (4-HC), where a sensitivity rate (# samples sensitive/total tested against agent) of 64% (95 % CI, 36.6-77.9%) was noted. This rate was significantly higher than with any other agent tested (p = 0.012, two sided McNemar's test) and was not affected by age, histology or disease status. We conclude that: (1) the FCA represents a feasible method for quickly assaying tumors for sensitivity to multiple chemotherapeutic agents; and (ii) malignant gliomas may be particularly sensitive to 4-HC.
BACKGROUND: Retrograde cerebral perfusion through the superior vena cava (SVC) has been proposed to protect the brain from ischaemic injury during profound hypothermic circulatory arrest (PHCA). Its contribution to cerebral protection is unclear. Furthermore, the addition of anaesthetic or vasodilating agents to the SVC perfusate to enhance brain protection, has never been described. METHODS: In three patients undergoing repair of the ascending aorta utilizing PHCA, the upper body was retrogradely perfused with cold (16 degrees C) blood through the SVC by the cardiopulmonary bypass pump. Electroencephalographic activity was monitored using a computerized electroencephalographic monitor (Cerebro Trac 2500, SRD). Perfusion pressure was measured at a port in the cannula connector. Etomidate or thiopentone was injected into the SVC perfusate to arrest reappearing electroencephalographic activity. Nitroglycerin or nitroprusside was injected into the perfusate to increase retrograde flow and maintain a constant perfusion pressure. RESULTS: During PHCA periods of up to 61 min, recurrent electroencephalographic activity was abolished by the retrograde administration of small boluses of etomidate (total 50 mg) or thiopentone (total 500 mg). Nitroprusside (100 micrograms) and nitroglycerin (2 micrograms.kg-1.min-1) increased retrograde flow from 220 to 550 and 660 ml.min-1, respectively, while maintaining perfusion pressure (25-26 mmHg). Recovery from anaesthesia and surgery was uneventful, with no adverse neurological sequelae. CONCLUSION: Injection of anaesthetic agents into the retrograde SVC perfusate during PHCA, can suppress reoccurring electroencephalographic activity and retrograde injection of vasodilators can facilitate an increase in perfusion. It is suggested that both may augment brain protection.
BACKGROUND: Recent studies indicate that during regional myocardial ischemia and subsequent reperfusion, volatile anesthetics may provide protection against free radical-related injury. The effect of halothane on free radical production during ischemia and reperfusion, in the canine heart, was investigated. The level of hydroxyl radical (.OH)-mediated conversion of salicylate to its dehydroxybenzoate derivatives (2,3-DHBA and 2,5-DHBA) was monitored. METHODS: Under general anesthesia, the heart was exposed through median sternotomy. Salicylate (100 mg/kg given intravenously) was administered 30 min before left anterior descending artery occlusion. Six dogs were studied using inhaled halothane (1.6%) 10 min before and during the 10-min ischemic period, followed by 50 min of reperfusion, and then they were compared with seven other dogs used as controls. Blood concentrations of salicylate, 2,3-DHBA and 2,5-DHBA, K+, lactate, oxygen content, and pH were monitored. RESULTS: An acute increase in the normalized concentrations of 2,3-DHBA and 2,5-DHBA was observed in the control animals during reperfusion. In contrast, halothane inhalation completely inhibited the production of both metabolites (P < 0.02), but 2,5-DHBA concentrations in the halothane-treated group were even less than the basal level (P < 0.05). The increase in lactate concentrations in the experimental animals was significantly less than that of controls (P < 0.05) and followed the same time-dependent pattern as the changes in K+ and pH. Halothane significantly decreased (P < 0.0001) the difference in oxygen content between coronary sinus and aortic root blood, suggesting decreased oxygen utilization during reperfusion. CONCLUSIONS: Halothane completely inhibited the production of .OH, and its administration may protect the heart from the deleterious effect of oxygen-derived reactive species, with attenuation of the metabolic response to ischemia.
OBJECTIVES: Although previous studies have shown physicians support advance directives, little is known about how they actually participate in decision-making. This study investigate (1) how much experience physicians have had discussing and following advance preferences and (2) how physicians perceive their role in the advance decision-making process. DESIGN: Mail survey conducted in 1993. SETTING: The Department of Veterans Affairs. PARTICIPANTS: A national probability sample of 1050 VA internists, family physicians, and generalists. MEASUREMENTS AND MAIN RESULTS: Questionnaires were returned by 67% of participants. In the last year, 79% stated they had discussed advance preference with at least one patient, and 19% had talked to more than 25. Seventy-three percent had used a written directive to make decisions for at least one incompetent patient. Younger age, board certification, spending less time in the outpatient setting, and personal experience with advance decision-making, were all associated independently with having advance preference discussions. Among physicians who had discussions, 59% said they often initiated the discussion, 55% said discussions often occurred in inpatient settings, and 31% said discussions often occurred in outpatient settings. Eighty-two percent of those responding thought physicians should be responsible for initiating discussions. Most would try to persuade a patient to change a decision that was not well informed (91%), not medically reasonable (88%), or not in the patient's best interest (88%); few would attempt to change decisions that conflicted with their own moral beliefs (14%). CONCLUSIONS: Physicians report that they are actively involved with their patients in making decisions about end-of-life care. Most say they have had recent discussions with at least some of their patients and feel that as physicians they should play a large and important role in soliciting and shaping patient preferences.
STUDY OBJECTIVE: To study the incidence of myocardial ischemia and related hemodynamic alterations in sedated patients undergoing fiberoptic bronchoscopy (FOB). DESIGN: Prospective study. SETTING: Tertiary care, university hospital. PATIENTS: Twenty-nine patients, age 50 years or older, undergoing elective FOB. INTERVENTIONS: Myocardial ischemia was assessed by continuous ECG monitoring beginning 30 min before, and until 2 h after FOB. MEASUREMENTS AND RESULTS: During FOB, there was a significant rise in heart rate (89+/-3 [mean+/-SE] to 120+/-4 beats/min) and fall in oxygen saturation (95+/-1 to 90+/-1%). There was no significant rise in systolic or diastolic BP. Five patients (17%) had myocardial ischemia during FOB that lasted 20+/-8 min. Their demographic and pre-FOB characteristics were not different from the other patients. Compared to baseline values, a significant rise in heart rate, a fall in oxygen saturation, and no significant change in BP were observed during FOB in patients, both with or without ischemia. Although not statistically significant, ischemia was associated with more protracted procedures. CONCLUSIONS: Myocardial ischemia may develop in elderly patients undergoing FOB. This observation encourages the routine use of ECG and oximetry during FOB, allowing for early intervention to prevent the dangerous combination of hypoxia, tachycardia, and myocardial ischemia. Moreover, this study suggests that methods to ensure oxygenation during FOB should be adhered to, and that the routine administration of atropine should be reconsidered.
BACKGROUND: Inherent limitations of conventional cytology often result in a failure to diagnose lymphomatous meningitis in cerebrospinal fluid (CSF) specimens from patients who actually have the disease. The development of polymerase chain reaction (PCR) techniques for the diagnosis of lymphoma based on the detection of clonal rearrangements of the immunoglobulin or T-cell receptor genes offers an alternative, DNA-based test for the diagnosis of lymphoma in the CSF. METHODS: In this retrospective study, 31 CSF specimens from 21 patients were examined by a PCR technique that can detect clonal immunoglobulin gene rearrangements. Twenty-four of the specimens came from 14 patients who eventually had definitive histologic or cytologic diagnoses of B-cell lymphoma. The other seven patients had other neurologic diagnoses, including two patients with reactive lymphocytosis, three with glioblastoma, one with metastatic carcinoma, and one with multi-infarct dementia. The results of the PCR examinations were compared with cytologic evaluation of the same CSF specimens. RESULTS: Five of seven specimens from patients with central nervous system lymphoma that were suspicious for, but not diagnostic of, lymphoma by conventional cytology were positive by PCR. Of 13 specimens from patients with lymphoma that showed no cytologic evidence of malignancy, 5 were positive by PCR. Two of four specimens for which conventional cytology showed definitive evidence of lymphoma were positive by PCR. Two specimens from patients with a reactive lymphocytosis showed a polyclonal pattern by PCR. Specimens from patients with other neurologic diseases were negative by PCR even when cytologically malignant (glioblastoma) cells were present in the specimen. CONCLUSIONS: PCR examination of CSF is practical, complements conventional cytology, and sometimes provides the correct diagnosis when conventional cytology yields only ambiguous results.
BACKGROUND: Myocardial protection during open heart surgery is based on administration of oxygenated blood cardioplegia, the preferred temperature of which is still under debate. The current randomized study was designed to prospectively evaluate the quality of myocardial protection and the functional recovery of the heart with either normothermic (group N) or hypothermic (group H) oxygenated blood cardioplegia. METHODS: Under continuous electrocardiographic Holter monitoring, 42 patients were randomly scheduled to receive either normothermic (33.5 degrees C) or hypothermic (10 degrees C) cardioplegia solutions during coronary bypass grafting surgery. Blood samples for creatinine phosphokinase, creatinine phosphokinase-MB, lactate, epinephrine, and norepinephrine were withdrawn during cardiopulmonary bypass via a coronary sinus cannula. RESULTS: Active cooling in group H on initiation of cardiopulmonary bypass was characterized by transition through ventricular fibrillation in 75% of patients, whereas in group N atrial fibrillation occurred in 65% of patients. On myocardial reperfusion, sinus rhythm spontaneously resumed in 95% of group N patients compared to 25% in group H (P = 0.0003). In the latter, 75% of patients developed ventricular fibrillation often followed by complete atrioventricular block, which necessitated temporary pacing for a mean duration of 168 +/- 32 min. Both groups showed a similar incidence of intraventricular block and ST segment changes. However, the incidence of ventricular premature beats in the first 16 h after cardiopulmonary bypass was significantly greater in group H (P < 0.05), 20 +/- 26/h, compared to 3 +/- 5/h in group N. Blood concentrations of lactate, creatinine phosphokinase, epinephrine, and norepinephrine increased gradually during the operation, but the differences between the groups were not significant. CONCLUSIONS: The current prospective human study suggests that the increased susceptibility for ventricular fibrillation and dysrhythmia, and the delayed recovery of the conduction system after hypothermic myocardial protection, are related to temperature-induced changes in vital cellular functions of the conduction tissue in the postischemic period. Both cardioplegic methods provide adequate myocardial protection but normothermic oxygenated blood cardioplegia may accelerate recovery of the heart after cardiopulmonary bypass.
Polyamines (PA) are derived from ornithine by the enzyme ornithine decarboxylase (ODC), which is activated very rapidly as acute and delayed responses to brain ischemia and trauma. Polyamines play a role in the disruption of the blood-brain barrier (BBB) in different pathological states. This study examined the effect of exogenous polyamines, administered intracerebrally (i.c.v.) or intracarotidly on BBB function. Putrescine, spermidine and spermine, given individually, were found to disrupt BBB integrity within 15 min of i.c.v. administration (p = 0.03; p = 0.0013; p = 0.042 vs saline treated rats, respectively). The effect was still evident after 1 h; however, since the saline treated rats also showed increased permeability of Evans blue at this time, there was no statistical difference between polyamines or saline treated rats 1 h post injection. When injected into the carotid artery, rapid increase in BBB permeability was found 1 min after putrescine and spermidine (p < 0.01 vs saline), with a slight decline at 15 min. A slower effect was noticed after spermine administration which reached significance only at 15 min. These results suggest a role for PA as mediators of vasogenic edema formation in the brain soon after brain injuries which induce increased production of these compounds.
The association of plasma cell myeloma and eosinophilia is rare. The authors describe a 49-year-old man with plasma cell myeloma and marked absolute peripheral blood eosinophilia, 109.7 x 10(9)/L. Analysis of his bone marrow revealed cytologically atypical plasma cells that expressed monotypic IgG lambda and marked eosinophilia with normal maturation. A combination of steroids and chemotherapy resulted in a significant and sustained decrease in his absolute eosinophil count and bone marrow plasma cells. Analysis of the patient's pre-therapy serum revealed immunoreactive interleukin-3 (IL-3), but not IL-5 or granulocyte/macrophage colony stimulating factor (GM-CSF). The post-therapy serum sample was negative. Immunohistochemical analysis of the plasma cells for IL-3 and IL-5 was negative. This review of the literature has revealed five cases of plasma cell myeloma associated with eosinophilia described previously. In two patients, the eosinophilia was attributed to drug therapy. In the remaining cases, the pathogenesis of the eosinophilia was unexplained. In this case, IL-3 secreted either by the neoplastic cells at a level below detection by immunohistochemistry or by other cells in response to the presence of plasma cell myeloma may have played a role in causing the eosinophilia.
Inflammatory pseudotumor (inflammatory fibroid polyp) of the ileum is a rare, usually solitary and polypoid lesion that frequently presents clinically as small-intestinal intussusception and obstruction. Regional lymph nodes are usually not involved. We describe an inflammatory pseudotumor of the ileum that was multifocal, not polypoid, and involved one regional lymph node. Grossly, two circumferential transmural nodules were separated by 8.5 cm of normal ileum. Microscopically, the lesion extended through the muscularis propria into peri-intestinal adipose tissue and involved one noncontiguous regional lymph node. The pseudotumor was composed of highly vascularized stroma with a mixture of spindle cells and chronic inflammatory cells including numerous eosinophils, lymphocytes, plasma cells, histiocytes, neutrophils, and multinucleated giant cells forming small granulomas. Immunohistochemically, the majority of spindle cells reacted with vimentin but not smooth-muscle, endothelial, or lymphoid markers. Ultrastructurally, the spindle cells had abundant rough endoplasmic reticulum, cytoplasmic filaments, and dense bodies consistent with myofibroblasts, plump endothelial cells (some with Weibel-Palade bodies), and chronic inflammatory cells. We prefer the term inflammatory pseudotumor to inflammatory fibroid polyp for the lesion in this case, since it was not polypoid and shared many histologic features with inflammatory pseudotumors arising at sites other than the gastrointestinal tract.