Incidence of brain metastasis according to patient race and primary cancer origin: a systematic review.

PURPOSE: A systematic review was conducted to investigate differences in incidence and primary origin of synchronous brain metastasis (sBM) in varying racial groups with different primary cancers. METHODS: Adhering to PRISMA 2020 guidelines a search was conducted using PubMed and Ovid databases for publications from January 2000 to January 2023, with search terms including combinations of "brain metastasis," "race," "ethnicity," and "incidence." Three independent reviewers screened for inclusion criteria encompassing studies clearly reporting primary cancer sites, patient demographics including race, and synchronous BM (sBM) incidence. RESULTS: Of 806 articles, 10 studies comprised of mainly adult patients from the United States met final inclusion for data analysis. Higher sBM incidence proportions were observed in American Indian/Alaska native patients for primary breast (p < 0.001), colorectal (p = 0.015), and esophageal cancers (p = 0.024) as well as in Asian or Pacific islanders for primary stomach (p < 0.001), thyroid (p = 0.006), and lung/bronchus cancers (p < 0.001) yet higher proportions in White patients for malignant melanoma (p < 0.001). Compared to White patients, Black patients had higher sBM incidence likelihood in breast cancer (OR = 1.27, p = 0.01) but lower likelihood in renal (OR = 0.46, p < 0.001) and esophageal cancers (OR = 0.31, p = 0.005). American Indian/Alaska native patients had a higher sBM likelihood (OR = 3.78, p = 0.004) relative to White patients in esophageal cancer. CONCLUSIONS: These findings reveal several comparative racial differences in sBM incidence arising from different primary cancer origins, underscoring a need for further research to explain these variations. Identifying the factors contributing to these disparities holds the potential to promote greater equity in oncological care according to cancer type.

Mechanisms of cryoablation: clinical consequences on malignant tumors.

While the destructive actions of a cryoablative freeze cycle are long recognized, more recent evidence has revealed a complex set of molecular responses that provides a path for optimization. The importance of optimization relates to the observation that the cryosurgical treatment of tumors yields success only equivalent to alternative therapies. This is also true of all existing therapies of cancer, which while applied with curative intent; provide only disease suppression for periods ranging from months to years. Recent research has led to an important new understanding of the nature of cancer, which has implications for primary therapies, including cryosurgical treatment. We now recognize that a cancer is a highly organized tissue dependent on other supporting cells for its establishment, growth and invasion. Further, cancer stem cells are now recognized as an origin of disease and prove resistant to many treatment modalities. Growth is dependent on endothelial cells essential to blood vessel formation, fibroblasts production of growth factors, and protective functions of cells of the immune system. This review discusses the biology of cancer, which has profound implications for the diverse therapies of the disease, including cryosurgery. We also describe the cryosurgical treatment of diverse cancers, citing results, types of adjunctive therapy intended to improve clinical outcomes, and comment briefly on other energy-based ablative therapies. With an expanded view of tumor complexity we identify those elements key to effective cryoablation and strategies designed to optimize cancer cell mortality with a consideration of the now recognized hallmarks of cancer.

The Rapid Development of Artificial Intelligence: GPT-4's Performance on Orthopedic Surgery Board Questions.

Advances in artificial intelligence and machine learning models, like Chat Generative Pre-trained Transformer (ChatGPT), have occurred at a remarkably fast rate. OpenAI released its newest model of ChatGPT, GPT-4, in March 2023. It offers a wide range of medical applications. The model has demonstrated notable proficiency on many medical board examinations. This study sought to assess GPT-4's performance on the Orthopaedic In-Training Examination (OITE) used to prepare residents for the American Board of Orthopaedic Surgery (ABOS) Part I Examination. The data gathered from GPT-4's performance were additionally compared with the data of the previous iteration of ChatGPT, GPT-3.5, which was released 4 months before GPT-4. GPT-4 correctly answered 251 of the 396 attempted questions (63.4%), whereas GPT-3.5 correctly answered 46.3% of 410 attempted questions. GPT-4 was significantly more accurate than GPT-3.5 on orthopedic board-style questions (P<.00001). GPT-4's performance is most comparable to that of an average third-year orthopedic surgery resident, while GPT-3.5 performed below an average orthopedic intern. GPT-4's overall accuracy was just below the approximate threshold that indicates a likely pass on the ABOS Part I Examination. Our results demonstrate significant improvements in OpenAI's newest model, GPT-4. Future studies should assess potential clinical applications as AI models continue to be trained on larger data sets and offer more capabilities. [Orthopedics. 2024;47(2):e85-e89.].

GPT-4 Artificial Intelligence Model Outperforms ChatGPT, Medical Students, and Neurosurgery Residents on Neurosurgery Written Board-Like Questions.

BACKGROUND: Artificial intelligence (AI) and machine learning have transformed health care with applications in various specialized fields. Neurosurgery can benefit from artificial intelligence in surgical planning, predicting patient outcomes, and analyzing neuroimaging data. GPT-4, an updated language model with additional training parameters, has exhibited exceptional performance on standardized exams. This study examines GPT-4's competence on neurosurgical board-style questions, comparing its performance with medical students and residents, to explore its potential in medical education and clinical decision-making. METHODS: GPT-4's performance was examined on 643 Congress of Neurological Surgeons Self-Assessment Neurosurgery Exam (SANS) board-style questions from various neurosurgery subspecialties. Of these, 477 were text-based and 166 contained images. GPT-4 refused to answer 52 questions that contained no text. The remaining 591 questions were inputted into GPT-4, and its performance was evaluated based on first-time responses. Raw scores were analyzed across subspecialties and question types, and then compared to previous findings on Chat Generative pre-trained transformer performance against SANS users, medical students, and neurosurgery residents. RESULTS: GPT-4 attempted 91.9% of Congress of Neurological Surgeons SANS questions and achieved 76.6% accuracy. The model's accuracy increased to 79.0% for text-only questions. GPT-4 outperformed Chat Generative pre-trained transformer (P < 0.001) and scored highest in pain/peripheral nerve (84%) and lowest in spine (73%) categories. It exceeded the performance of medical students (26.3%), neurosurgery residents (61.5%), and the national average of SANS users (69.3%) across all categories. CONCLUSIONS: GPT-4 significantly outperformed medical students, neurosurgery residents, and the national average of SANS users. The mode's accuracy suggests potential applications in educational settings and clinical decision-making, enhancing provider efficiency, and improving patient care.

Diagnostic accuracy of telestroke consultation: a Louisiana based tele-network experience.

Background and purpose: Telestroke has grown significantly since its implementation. Despite growing utilization, there is a paucity of data regarding the diagnostic accuracy of telestroke to distinguish between stroke and its mimics. We aimed to evaluate diagnostic accuracy of telestroke consultations and explore the characteristics of misdiagnosed patients with a focus on stroke mimics. Methods: We conducted a retrospective study of all the consultations in our Ochsner Health's TeleStroke program seen between April 2015 and April 2016. Consultations were classified into one of three diagnostic categories: stroke/transient ischemic attack, mimic, and uncertain. Initial telestroke diagnosis was compared with the final diagnosis post review of all emergency department and hospital data. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (LR+) and negative likelihood ratio (LR-) for diagnosis of stroke/TIA versus mimic were calculated. Area under receiver-operating characteristic curve (AUC) analysis to predict true stroke was performed. Bivariate analysis based on the diagnostic categories examined association with sex, age, NIHSS, stroke risk factors, tPA given, bleeding after tPA, symptom onset to last known normal, symptom onset to consult, timing in the day, and consult duration. Logistic regression was performed as indicated by bivariate analysis. Results: Eight hundred and seventy-four telestroke evaluations were included in our analysis. Accurate diagnosis through teleneurological consultation was seen in 85% of which 532 were strokes (true positives) and 170 were mimics (true negatives). Sensitivity, specificity, PPV, NPV were 97.8, 82.5, 93.7 and 93.4%, respectively. LR+ and LR- were 5.6 and 0.03. AUC (95% CI) was 0.9016 (0.8749-0.9283). Stroke mimics were more common with younger age and female gender and in those with less vascular risk factors. LR revealed OR (95% CI) of misdiagnosis for female gender of 1.9 (1.3-2.9). Lower age and lower NIHSS score were other predictors of misdiagnosis. Conclusion: We report high diagnostic accuracy of the Ochsner Telestroke Program in discriminating stroke/TIA and stroke mimics, with slight tendency towards over diagnosis of stroke. Female gender, younger age and lower NIHSS score were associated with misdiagnosis.

The Multivariate Relationship Between Primary Anterior Cruciate Ligament Reconstruction Timing and Revision Rates: A 10-Year Analysis.

Background and objective The optimal timing of anterior crucial ligament reconstruction (ACLR) remains a matter of controversy. A revision procedure is performed to improve knee function, correct instability, and enable a safe return to daily function when primary ACLR fails. The present study aimed to determine if the timing of primary ACLR is predictive of revision surgery. Methods All patients who underwent primary ACLR at the West Virginia University from January 2008 to December 2018 were identified. Patients were initially grouped into early (≤30 days) and late (>30 days) ACLR based on the onset of the initial injury. The major outcome measure of this study was the incidence of revision ACLR following primary ACLR. Results A total of 233 primary ACLRs were included. The incidence of ACLR revisions was 9.4%. The timing of primary ACLR, when categorized into early and late ACLRs, was not found to influence revision risk (p=0.384). Additionally, the damaged anatomical structures based on the postoperative diagnosis at the time of ACLR did not influence the odds of revision ACLR (p=0.9721). Conclusion Our study found that the timing of primary ACLR did not influence the revision rates when categorizing primary surgery time into early and late subgroups.

Status of US Emergency Medical Service Protocols Regarding Pre-Transfer Cooling for Exertional Heat Stroke.

OBJECTIVE:  Exertional heat stroke (EHS) is a significant cause of morbidity and mortality in athletes and active individuals. In the field, initial management of exertional heat illness is based on rapid whole-body cooling. Cold-water immersion (CWI) is considered the superior cooling modality for EHS treatment. However, there often is a disconnect between the sports medicine community and the emergency medical service (EMS) community. Well-written emergency action plans may fail if EMS protocols do not allow for CWI in initial management. This is the first study to look at the current national EMS protocols regarding prehospital management of EHS. The purpose of our study was to assess the status of heat illness protocols regarding CWI for EHS in all 50 states plus Washington, DC.  Methods: An internet search was performed to find EHS protocols. Statewide protocols were preferred. Several parameters were recorded for each protocol including whether: 1) CWI was the recommended cooling treatment for EHS and 2) CWI was explicitly permitted to be completed prior to transportation. RESULTS:  We found nine of the 51 protocols, or 17.6%, explicitly recommended CWI and 11 of the 51, or 21.6%, specifically instructed EMS personnel to complete CWI or cooling methods prior to transport. However, six protocols, or 11.8%, provided the recommendation instructing some variation of the phrase "do not delay transport to cool the patient." CONCLUSION:  Despite the medical literature endorsing CWI as the most effective treatment modality in a prehospital setting for exertional heat illness, EMS protocols largely fail to reflect this which leads to mismanagement and inadequate care of EHS patients. While CWI is not always available, all EMS protocols should include a systematic practical guideline for a heat illness patient when employing cooling treatment with an emphasis on CWI when available as the preferred treatment technique for EHS and the concept of "cool first, transport second."

Experimental cryosurgery investigations in vivo.

Cryosurgery is the use of freezing temperatures to elicit an ablative response in a targeted tissue. This review provides a global overview of experimentation in vivo which has been the basis of advancement of this widely applied therapeutic option. The cellular and tissue-related events that underlie the mechanisms of destruction, including direct cell injury (cryolysis), vascular stasis, apoptosis and necrosis, are described and are related to the optimal methods of technique of freezing to achieve efficacious therapy. In vivo experiments with major organs, including wound healing, the putative immunological response following thawing, and the use of cryoadjunctive strategies to enhance cancer cell sensitivity to freezing, are described.

TGFß1-induced expression of caldesmon mediates epithelial-mesenchymal transition.

Epithelial-mesenchymal transition (EMT) is an important process that mediates organ development and wound healing, and in pathological contexts, it can contribute to the progression of fibrosis and cancer. During EMT, cells exhibit marked changes in cytoskeletal organization and increased expression of a variety of actin associated proteins. Here, we sought to determine the role of caldesmon in mediating EMT in response to transforming growth factor (TGF)-ß1. We find that the expression level and phosphorylation state of caldesmon increase as a function of time following induction of EMT by TGFß1 and these changes in caldesmon correlate with increased focal adhesion number and size and increased cell contractility. Knockdown and forced expression of caldesmon in epithelial cells reveals that caldesmon expression plays an important role in regulating the expression of the myofibroblast marker alpha smooth muscle actin. Results from these studies provide insight into the role of cytoskeletal associated proteins in the regulation of EMT and may suggest ways to target the cell cytoskeleton for regulating EMT processes.

Issues critical to the successful application of cryosurgical ablation of the prostate.

The techniques of present-day cryosurgery performed with multiprobe freezing apparatus and advanced imaging techniques yield predictable and encouraging results in the treatment of prostatic and renal cancers. Nevertheless, and not unique to cryosurgical treatment, the rates of persistent disease demonstrate the need for improvement in technique and emphasize the need for proper management of the therapeutic margin. The causes of persistent disease often relate to a range of factors including selection of patients, understanding of the extent of the tumor, limitations of the imaging techniques, and failure to freeze the tumor periphery in an efficacious manner. Of these diverse factors, the one most readily managed, but subject to therapeutic error, is the technique of freezing the tumor and appropriate margin to a lethal temperature [Baust, J. G., Gage, A. A. The Molecular Basis of Cryosurgery. BJU Int 95, 1187-1191 (2005)]. This article describes the recent experiments that examine the molecular basis of cryosurgery, clarifies the actions of the components of the freeze-thaw cycle, and defines the resultant effect on the cryogenic lesion from a clinical perspective. Further, this review addresses the important issue of management of the margin of the tumor through adjunctive therapy. Accordingly, a goal of this review is to identify the technical and future adjunctive therapeutic practices that should improve the efficacy of cryoablative techniques for the treatment of malignant lesions.

Targeted induction of apoptosis via TRAIL and cryoablation: a novel strategy for the treatment of prostate cancer.

Adjuvant therapies contribute to the successful treatment of cancer. Our previous reports have shown that combining cryoablation with cytotoxic agents enhances cell death. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytotoxic agent that preferentially induces apoptosis in a variety of human cancer cells. Human prostate cancer cells (PC-3) are resistant to many cytodestructive agents, including cryoablation and TRAIL. Here, we evaluated the effects of TRAIL combined with cryoablation on PC-3 and normal prostate (RWPE-1) cell death. Exposure of PC-3 cells to freezing (-10 degrees C) or TRAIL (500 ng/ml) results in minimal cell death, whereas a complete loss of viability is observed with the simultaneous combination. The synergistic effect was found to be due to a marked increase in apoptosis. Western blot analysis revealed a significant level of caspase-8 and -3 cleavage between 12 and 24 h post-exposure. Caspase activation assays provided similar results and also indicated a role for caspase-9. Inhibitors to caspase-8 and -9 along with a pan-caspase inhibitor were incorporated to determine which pathway was necessary for the combined efficacy. Inhibition of caspase-8 significantly blocked the combination-induced cell death compared to cells that did not receive the inhibitor (63% compared to 10% viable). The addition of the caspase-9 inhibitor resulted in only a minimal protection. Importantly, the combination was not effective when applied to normal prostate cells. The results describe a novel therapeutic model for the treatment of prostate cancer and provide support for future in vivo studies.

Attitudes toward the discontinuation of female genital cutting among men and women in Guinea.

OBJECTIVE: To investigate socioeconomic correlates of and gender differences in attitudinal support for the discontinuation of FGC in Guinea. METHOD: Data from structured interviews of men aged 15-59 and women aged 15-49 years in the 1999 Demographic and Health Survey and multiple logistic regression methods were used to examine the relationship of socioeconomic factors and gender to attitudinal support for the discontinuation of FGC. RESULT: More than 9 out of 10 women had undergone FGC. Attitudinal support for FGC discontinuation was more prevalent among men than women. The odds of supporting the discontinuation of FGC were negatively related to beliefs in social approval of and religious support for FGC and its enhancement of women's marriageability, the number of perceived advantages of FGC, and women's low socioeconomic status. CONCLUSION: Community education, improvements in women's socioeconomic status and traditional and religious leader involvement would be critical for FGC eradication.

Re-purposing cryoablation: a combinatorial 'therapy' for the destruction of tissue.

It is now recognized that the tumor microenvironment creates a protective neo-tissue that isolates the tumor from the various defense strategies of the body. Evidence demonstrates that, with successive therapeutic attempts, cancer cells acquire resistance to individual treatment modalities. For example, exposure to cytotoxic drugs results in the survival of approximately 20-30% of the cancer cells as only dividing cells succumb to each toxic exposure. With follow-up treatments, each additional dose results in tumor-associated fibroblasts secreting surface-protective proteins, which enhance cancer cell resistance. Similar outcomes are reported following radiotherapy. These defensive strategies are indicative of evolved capabilities of cancer to assure successful tumor growth through well-established anti-tumor-protective adaptations. As such, successful cancer management requires the activation of multiple cellular 'kill switches' to prevent initiation of diverse protective adaptations. Thermal therapies are unique treatment modalities typically applied as monotherapies (without repetition) thereby denying cancer cells the opportunity to express defensive mutations. Further, the destructive mechanisms of action involved with cryoablation (CA) include both physical and molecular insults resulting in the disruption of multiple defensive strategies that are not cell cycle dependent and adds a damaging structural (physical) element. This review discusses the application and clinical outcomes of CA with an emphasis on the mechanisms of cell death induced by structural, metabolic, vascular and immune processes. The induction of diverse cell death cascades, resulting in the activation of apoptosis and necrosis, allows CA to be characterized as a combinatorial treatment modality. Our understanding of these mechanisms now supports adjunctive therapies that can augment cell death pathways.

Inhibition of transplant rejection by pretreatment of xenogeneic pancreatic islet cells with anti-ICAM-1 antibodies.

Cognate recognition of antigen-presenting cells by antigen-specific T cells is critically dependent on non-cognate adhesive interactions. For instance, several studies have shown that in vivo anti-LFA-1 plus anti-ICAM-1 mAb treatment results in prolongation of allograft survival. We have developed a xenogeneic islet transplant model to investigate the role of various adhesion interactions in the xenogeneic response and study the effect of pretreating donor tissue with immunosuppressive drugs. Pancreatic islet cells were pretreated in vitro with anti-human ICAM-1 mAb, transplanted under the renal capsule of diabetic B6 mice in the absence of systemic immunosuppression and examined for long-term xenograft acceptance. The survival of human islets pretreated with anti-human ICAM-1 was significantly prolonged (MST = 53 days, with 40% of grafts surviving > 100 days). In contrast, the survival of human islets pretreated with the control antibody was similar to those of nontreated islets (MST = 7 days). A massive lymphocyte infiltrate into control xenografts was observed at 5 days post-transplant. In contrast, a lymphocyte infiltrate did not appear in the anti-ICAM-1-treated islets for at least 11 days. Only mAbs specific for the LFA-1 binding epitope of ICAM-1 were found to inhibit a mixed islet/lymphocyte reaction in vitro and block graft rejection in vivo. However, graft prolongation is not accompanied by systemic tolerance. Mice transplanted simultaneously with human islet cells treated with control Ig (left kidney) or anti-ICAM-1 (right kidney) rejected the control islets but not anti-ICAM-1-treated islets. These results suggest that the LFA-1/ICAM-1 interaction is a critical component for xenograft rejection and, more important, that pretreatment of islet tissue with anti-adhesion molecule antibodies can profoundly alter graft recognition and rejection in the absence of any systemic drug therapy. However, graft prolongation is not accompanied by systemic tolerance induction.

Maternal effects on the development of social rank and immunity trade-offs in male laboratory mice (Mus musculus).

Social status in randomly constituted groups of male CFLP mice was predictable from early suckling behaviour and rate of weight gain in natal litters. High-ranking males were those that had suckled on more anterior teats and gained weight more quickly. Rank was not predicted by any measures of sibling interaction or hormone (testosterone, corticosterone) concentration. Aggressiveness in eventual high-rankers was associated negatively with the proportion of males in the litter at birth and the amount of maternal attention received. Aggressive social relationships within natal litters did not predict polarized rank relationships in randomized groups. Nevertheless, while still in their natal litters, and in the absence of aggressive rank relationships, eventual rank categories showed the same difference in modulation of testosterone concentration in relation to current immunocompetence (low-rankers modulating, high-rankers not), as has repeatedly been found in randomized groups by earlier studies. The role of maternal condition in determining rank-related life-history development in male mice is discussed.

The role of parasite-induced immunodepression, rank and social environment in the modulation of behaviour and hormone concentration in male laboratory mice (Mus musculus).

Peripheral immune responsiveness in male laboratory mice was reduced by infection with the trichostrongyloid nematode Heligmosomoides polygyrus. Responsiveness was also lower among high-ranking (aggressive) males regardless of infection status. Reduced responsiveness in both infected animals and high rankers was associated with elevated serum corticosterone concentration (a potential immunodepressant) and was compounded among high-ranking males by subsequent high aggressiveness. As in previous experiments, only low rankers modulated testosterone secretion in relation to current immunocompetence and corticosterone concentration. The lack of any downregulation of aggression in response to parasite-induced immunodepression contrasted with previous results using antithymocyte serum and may be due to the more localized nature of immunodepression during H. polygyrus infection. However, the additional increase in corticosterone concentration resulting from exposure to female odour and destabilized aggressive social relationships did result in downregulation of aggression among high rankers and of testosterone among mice generally, suggesting that modulation rules of thumb are at least partly dependent on the proximate cues associated with immunodepression.

Verapamil cardioplegia: improved myocardial preservation during global ischemia.

To determine whether the calcium antagonist verapamil can produce satisfactory myocardial preservation during global ischemia, we studied three groups of eight dogs. Serial left ventricular biopsy specimens were taken for adenosine triphosphate and creatine phosphate content. Arterial and coronary sinus blood samples were obtained for lactate and oxygen content determination prior to ischemia, immediately after the ischemic interval, and after a 30 minute reperfusion period. Starling and isovolumetric ventricular function curves were determined prior to ischemic arrest and after 45 minutes of reperfusion. All animals were systemically cooled to 25 degrees C, and the aorta was clamped for 120 minutes. Group I had a potassium cardioplegic solution (30 mEq/L) chilled to 4 degrees C and injected into the aortic root. The initial dose was 200 ml and an additional 100 ml was infused at 20 minute intervals. Group II had a solution containing verapamil (0.15 mg/kg/L), diluted in Ringer's solution (4 degrees C), injected into the aortic root. The initial and subsequent doses were as in Group I. Group III received the same solution as Group II, but at room temperature. Alterations in lactate metabolism were not significantly different in any of the three treatment groups. A reduction in oxygen consumption was seen in Group III, but was not found to be statistically significant. However, the reduction in coronary flow at the end of reperfusion was statistically significant in Group III (p less than 0.05). Verapamil given at room temperature resulted in poor preservation of left ventricular function and high-energy stores. Verapamil combined with extreme hypothermia (Group II) provided excellent preservation of left ventricular compliance and contractility. Cold verapamil cardioplegia was superior to potassium cardioplegia for the preservation of adenosine triphosphate.

Noninvasive screening for asymptomatic carotid artery disease prior to cardiac operation. Experience with 500 patients.

Five hundred patients scheduled for cardiac operations underwent preoperative screening for asymptomatic carotid artery disease by means of the Gee ocular pneumoplethysmograph (OPG). Only patients with abnormal OPG measurements (5 mm Hg difference or greater in ophthalmic artery pressures or 0.69 or less ophthalmic artery/brachial artery pressure ratio) had cerebral angiography regardless of the presence or absence of a carotid bruit. Thirty-two patients (6.4%) were found to have carotid bruits. Nine patients had abnormal OPG measurements. Cerebral angiograms disclosed that six of these patients had significant (greater than 50%) carotid artery stenosis, and endarterectomy was performed prior to cardiac operation without incident. Nine other patients without carotid bruits had abnormal OPG measurements, and they also underwent cerebral angiography. Angiograms revealed significant carotid artery stenosis in three patients and prophylactic endarterectomy was performed. Twenty-three patients with carotid artery bruits and normal OPG measurements did not have cerebral angiography prior to the cardiac procedure. The incidence of stroke in this series of 500 patients was 0.4% (two patients). The clinical management of patients with asymptomatic carotid artery disease and coronary artery disease was facilitated by the use of noninvasive screening for the evaluation of carotid artery bruits. Patients with hemodynamically insignificant carotid disease, verified by OPG measurements, can be spared the risk and cost of cerebral angiography. Patients without clinical signs of carotid artery disease can also be identified.

Perioperative preservation of myocardial ultrastructure and high-energy phosphates in man.

To establish whether hypothermic crystalloid potassium cardioplegia given in multidose fashion provides adequate preservation of myocardial ultrastructure and high-energy phosphates, we studied 25 patients with an ejection fraction of 50% or higher who were undergoing cardiac procedures. Eight patients had three biopsy specimens taken from the left ventricular apex for determination of adenosine triphosphate (ATP) and creatine phosphate (CP). Specimens were taken immediately prior to aortic cross-clamping, immediately after the release of the aortic cross-clamp, and 30 minutes after the release of the cross-clamp. Seventeen patients had six specimens taken form the left ventricular apex at the above-stated times, three for ATP and CP determination and three additional specimens for electron microscopy. One patient had a small perioperative infarction and another patient died on the fifth postoperative day of an aortic dissection. The mitochondria on the electron microscopic specimens were graded on a scale from 0 to 4 (4 = severe changes). There was no significant difference in the mitochondrial scores. The preservation oh high-energy phosphates was less complete. ATP was reduced to 78% (3.4.2) of control and CP was reduced in the immediate postclamp period to 32% (081/2.5)of control. The difference are particularly significant if one looks at patients whose aortic cross-clamp time was 90 minutes or more (12 patients). In this group, ATP an CP preservation were 71% of control (3.33/4.60 mmoles/kg. wet weight) and 53% of control (l.48/2.81), 30 minutes after clamp removal (p equal to or less than 0.01). We conclude that hypothermic potassium cardioplegia gives excellent preservation of the myocardial ultrastructure in man. However, the preservation of high-energy phosphates with this technique is imperfect.

Cryosurgical treatment of the eyelids and lacrimal drainage ducts of the rhesus monkey. Course of injury and repair.

Freezing injuries were produced on the eyelids and lacrimal drainage systems in ten rhesus monkeys. The instrumentation produced both single and double freezing cycles at tissue temperatures of -30 and -60 degrees C. The extent of injury and the course of repair were evaluated by clinical observation and by histologic examination of tissue specimens removed at intervals up to three months after freezing. Both cryosurgical techniques produced necrosis of the tissues, but injury was less with single freezing cycles at -30 degrees C. The course of repair was favorable. Even at the three-month observation period, when healing was complete, there was minimal-clinical or histologic evidence of canalicular obstruction or other periocular complications.