The role of the calcium-sensing receptor in bone biology and pathophysiology.

Bone cells, particularly osteoblasts and osteoclasts, exhibit functional responses to calcium (Ca(2+)). The identification of the calcium-sensing receptor (CaR) in parathyroid glands as the master regulator of parathyroid hormone (PTH) secretion proved that cells could specifically respond to changes in divalent cation concentration. Yet, after many years of study, it remains unclear whether this receptor, which has also been identified in bone, has functional import there. Various knockout and transgenic mouse models have been developed, but conclusions about skeletal phenotypes remain elusive. Complex endocrine feedback loops involving calcium, phosphorus, vitamin D, and PTH confound efforts to isolate the effects of a single mineral, hormone, or receptor and most models fail to account for other local factors such as parathyroid hormone related protein (PTHrP). We review the relevant mouse models and discuss the importance of CaR in chondrogenesis and osteogenesis. We present the evidence for a non-redundant role for CaR in skeletal mineralization, including our experience in patients with activating CaR mutations. Additionally, we review emerging research on the importance of the CaR to the regulation of serum calcium homeostasis independent of PTH, the role of the CaR in the hematopoietic stem cell niche with implications for bone marrow transplant, and early evidence that implies a role for the CaR as a factor in skeletal metastasis from breast and prostate cancer. We conclude with a discussion of drugs that target the CaR directly either as agonists (calcimimetics) or antagonists (calcilytics), and the consequences for bone physiology and pathology.

Splenic injury after intraoperative transesophageal echocardiography.

A 55-year-old woman underwent coronary artery bypass grafting and mitral valve repair using intraoperative transesophageal echocardiography (TEE). Postoperatively she had hemodynamic instability associated with an increase in abdominal size and a drop in hemoglobin. At laparotomy, a splenic hilar laceration was discovered, which was presumed to be associated with intraoperative TEE. She underwent emergent splenectomy. This case demonstrates that although rare, serious complications can occur with TEE.

Effect of autotransfusion on fibrinolysis in open heart patients.

Autotransfused blood is often used as an alternative to banked blood. The fibrinolytic consequences of autotransfused blood are undefined. This prospective study was designed to determine the effect of intraoperative autotransfused blood on fibrinolysis and other coagulation parameters. Ten consecutive patients undergoing cardiopulmonary bypass (CPB) for open-heart procedures were studied. All patients received autotransfused blood intraoperatively and tolerated the procedure. Blood samples were taken preoperatively, intraoperatively, and at 6, 12, and 24 hours postoperatively. Coagulation parameters including prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen, fibrin degradation products, and D-dimer levels were measured at each time point. In addition, the quantity of autotransfused blood and additional standard blood products were recorded. Nonparametric repeated measures analyses with post hoc tests adjusted using the Bonferroni correction were used to analyze the data. Mean PT increased from 13.9 +/- 3.0 seconds preoperatively to 15.7 +/- 1.6 seconds intraoperatively, but then gradually declined to 14.5 +/- 1.1 seconds 24 hours postoperatively. A similar temporal pattern was observed for PTT, which reached a peak of 55.7 +/- 33.0 seconds intraoperatively from a preoperative baseline of 44.0 +/- 15.3 seconds. Adjusted post hoc comparisons of fibrinogen levels indicated a statistically significant difference between preoperative and 6 hour postoperative medians, (p < .0083). Fibrin degradation products had a modest and nonsignificant decrease over the 24-hour study period, (from 12.6 +/- 6.7 mcg/mL preoperatively to 9.0 +/- 1.6 mcg/ml 24 hours postoperatively), while D-dimer levels rose from a baseline of 0.54 +/- 0.09 mcg/mL to 0.98 +/- 0.48 mcg/mL 6 hours postoperatively, but declined nearly to baseline by 24 hours postoperatively, (0.62 +/- 0.11 mcg/mL). We conclude that although autotransfused blood may activate the fibrinolytic pathway, its use remains safe and does not require the use of additional banked blood products.

Intraoperative flow rate measurements of T-grafts: calculating a flow reserve.

OBJECTIVE: To evaluate the inflow of the left internal thoracic artery (LITA) and the effect of adding a radial artery T-graft to distal LITA flow, and to calculate the LITA flow reserve. METHODS: Twenty-two patients underwent myocardial revascularization using the radial artery-LITA T-graft in which intraoperative flow measurements were recorded. An ultrasonic flowmeter was used to directly measure flow rates in the T-graft: 1) before completion of the distal anastomoses to measure maximum flow rates (free flow), and 2) after completion of distal anastomoses. RESULTS: The mean free flow rates of the LITA alone, radial artery graft alone, and T-graft (total flow) were 104 +/- 70, 151 +/- 89, and 230 +/- 102 ml/min, respectively. The mean flow rates on bypass of the distal LITA, radial artery graft, and T-graft after the distal anastomoses were completed were 24 +/- 16, 32 +/- 27, and 63 +/- 29 ml/min, respectively. The mean T-graft flow off bypass was 66 +/- 29 ml/min. The mean flow reserve was 70%. CONCLUSION: The LITA has a flow reserve by which proximal flow rates will increase to accommodate the addition of a radial artery T-graft without compromising LITA flow distal to the T anastomosis.

Profound hypothermia and circulatory arrest in excision of renal cell carcinoma invading the vena cava.

Two patients with renal cell carcinoma invading the inferior vena cava to the level of the right atrium underwent complete excision of their renal tumours. Clearance of the caval extension was accomplished using cardiopulmonary bypass, profound hypothermia and circulatory arrest. The use of these techniques visually improved the operative field without extending operating time. Profound hypothermia and circulatory arrest do not increase postoperative morbidity or mortality and offer the best opportunity for cure.

Circulatory support after coronary artery surgery.

An important change in the pattern of pharmacologic and mechanical circulatory support following coronary artery surgery has been noted in Newfoundland. The authors studied two groups of patients: group 1, 119 patients who underwent coronary artery bypass procedures from 1975 to 1978 and group 2, 344 similar patients studied from 1979 to 1982. Both groups of patients had similar left ventricular function and similar numbers of grafts per patient were inserted (group 1, 2.6; group 2, 2.8). There was a great reduction in the need for perioperative circulatory support (group 1, 34%; group 2, 6%), associated with a notable reduction in the rate of myocardial infarction perioperatively (group 1, 24%; group 2, 4.9%). This improvement resulted from the routine use of invasive hemodynamic monitoring and cold blood cardioplegia in group 2 patients.

Coronary artery steal secondary to coronary arteriovenous fistula.

Coronary arteriovenous fistula in adults may be associated with angina pectoris. It has been suggested that the cause of the angina is a coronary artery steal of blood into the fistula but this has not been demonstrated. To study its hemodynamics the authors describe two cases of coronary artery fistula. They discuss the use of radionuclide angiography in this setting. The surgical technique is outlined and the use of intraoperative electrocardiographic monitoring is emphasized.

Intermittent venting of the left ventricle.

A technique is described for intermittent decompression of the left ventricle. This method provides all of the advantages of left ventricular venting while eliminating the hazards. The technique is most advantageous in coronary artery operations.

Sleeve lobectomy for carcinoma of the lung.

Sleeve lobectomy for non-oat cell carcinoma involving a major bronchus preserves functioning lung tissue and, in carefully selected patients, provides long-term survival comparable to pneumonectomy. Seventy patients underwent sleeve lobectomy between 1967 and 1978. Twenty-seven patients were considered compromised (Group I) because they had severe respiratory impairment which contraindicated pneumonectomy. Forty-three patients were considered uncompromised (Group 2) and underwent elective sleeve lobectomy. Seventy patients with a similar non-oat cell carcinoma involving the proximal bronchi underwent pneumonectomy (Group 3) during this period. Perioperative complications occurred more frequently in Group 1 (59%) than in Group 2 (21%) or Group 3 (23%). Both periopeative mortality rate and the incidence of bronchial disruption (bronchovascular and bronchopleural fistulas) were higher in Group I (19% and 22%) than in Group 2 (9% and 5%) or Group 3 (3% and 7%). Survival depended primarily on the surgeon's ability to perform a complete resection of the tumor. An incomplete resection resulted when tumor was found in the highest lymph node or in the last bronchial resection margin when paraffin sections were reviewed. The 5 year survival rate was 18% for compromised patients (Group 1) who underwent complete resection, and there were no survivors among patients undergoing incomplete resections. Uncompromised patients ( Group 2) had a 5 year survival rate of36% with complete and 12% with incomplete resections. Pneumonectomy patients (Group 3) had a 64% 5 year survival rate with a complete resection and 16% with an incomplete resection. The stage of the disease at the time of operation had a profound effect on the survivail. There was no difference inthe 5 and 8 year survival rates between uncompromised patients undergoing sleeve resection ( Group 2) and patients undergoing peneumonectomy (Group 3) for comparable stage of their disease. A careful pre- and postoperative functional assessment revealed that pulmonary performance was improved in 44% of Group 1, 63% of Group 2, and only 14% of Group 3 patients. Patients wiht impaired pulmonary reserve underwent sleeve lobectomy with an adequate disease-free interval when complete tumor excision was possible. Uncompromised patients whose extensive disease required incomplete resection had palliation by sleeve lobectomy equivalent to that by pneumonectomy. When complete t-mor resection was possible, patients with uncompromised pulmonary reserve had a perioperative complication rate and long-term survival equivalent to that of pneumonectomy while preserving pulmonary parenchyma, which permitted an improvement in postoperative pulmonary performance.

Morphological findings in idiopathic calcification of the ascending aorta and aortic valve affecting a young woman.

The pathology of a case of idiopathic calcification affecting the ascending aorta in a young woman is presented. A varying width of media throughout the aorta and extending into its proximaques of calcium, found in the acellular media, were confined to the ascending aorta. No inflammatory or reparative reaction was seen in the vessel wall. Electron microscopically, the calcium seemed to have an affinity for elastic tissue elements of all sizes and the mode of deposition appeared to be by 'avenues' of the microfibrillar component. Possible pathogenetic mechanisms are discussed.

Tumor invasion of the upper inferior vena cava: the use of profound hypothermia and circulation arrest as a surgical adjunct.

Two children presented with abdominal tumors invading the upper inferior vena cava. To facilitate removal of the tumors, cardiopulmonary bypass with profound hypothermia and circulation arrest were utilized. This technique simplifies tumor excision and is worthwhile even in children with advanced malignant disease.

Aortocoronary bypass made possible by coronary endarterectomy.

Thirty bypass grafts to coronary arteries were made possible by manual core endarterectomy. The overall patency rate of the grafts was 57%, which is less than the patency rate of bypass grafts to nonendarterectomized vessels (75 to 80%). In the perioperative period and during follow-up to 29 months there was no increase in mortality or morbidity even when the endarterectomized vessel subsequently became occluded. These results represent early technical experience. Routine anticoagulant therapy in the postoperative period, to prevent early occlusion, was not used. The results of this and other studies suggest that coronary endarterectomy with bypass grafting is a useful procedure in situations where the coronary artery is so severely obstructed that standard saphenous vein bypass grafting cannot be performed; the procedure is superior to coronary endarterectomy alone.

Carinal resection. A report of two cases and a description of the anesthetic technique.

Two cases of carinal tumor managed by resection and primary anastomosis are presented. Their course is discussed and a description of an anesthetic technique which obviates the need for cardiopulmonary bypass is presented. The principles of carinal surgery are discussed, emphasizing expert anesthesia and resection line control by frozen-tissue examination.