Evidence for P2-purinoceptors on human osteoblast-like cells.

ATP released from damaged cells or by controlled secretion could be an important factor in the formation or remodeling of bone. In a variety of other tissues ATP has been shown to control cellular processes by acting on P2-purinoceptors and activating the calcium signaling pathway. Here we demonstrate for the first time that extracellular ATP increases the intracellular free calcium [Ca2+]i concentration in normal human osteoblasts and in SaOS-2 cells, a human osteosarcoma-derived cell line, but not in ROS 17/2.8 cells. The ATP-induced increase in [Ca2+]i was dose dependent, and the concentrations of ATP required were similar to those reported to regulate cellular functions in other cell types. Although ATP is metabolized rapidly by bone cells, the effects on [Ca2+]i appeared to be mediated directly by ATP rather than one of its metabolites. Adenosine 3-thiotriphosphate, a nonhydrolyzable analog of ATP, induced similar changes in [Ca2+]i. This indicates that P2-purinoceptors are present on osteoblast-like cells and that extracellular ATP from various sources might be an important factor in the regulation of osteoblast functions.     

A SAFE,NEW APPROACH TO ESTABLISHING A PNEUMOPERITONEUM AT LAPAROSCOPY

The traditional method of establishing a pneumoperitoneum before laparoscopic surgery is via a Verres needle inserted in the midline below the umbilicus while tenting the abdominal wall with the hand. A new approach is described in which preliminary surgical exposure and tenting of the linea alba immediately above the umbilicus is achieved before needle insertion through the superior margin of the umbilical ring. The advantages of this new technique over the conventional method are discussed. Further technical features important in the safe formation of the pneumoperitoneum are emphasized.     

Long term continuous domiciliary oxygen therapy by transtracheal catheter.

Long term continuous oxygen therapy improves prognosis in patients with hypoxaemic chronic airflow limitation. Transtracheal delivery of oxygen permits adequate oxygenation of such patients at lower flow rates than are required for delivery by nasal cannulas, thus increasing the time for which portable oxygen cylinders can be used and improving the efficacy of domiciliary oxygen concentrators in patients with refractory hypoxaemia. In a study of the long term acceptability and risks of transtracheal oxygen in 37 patients, with a total follow up of 595 patient-months, most patients reported symptomatic benefit and four have used transtracheal oxygen successfully for more than four years. Problems have included surgical emphysema (4 patients), catheter fracture (9), local infection (34), and catheter dislodgement (21); but these have been relatively infrequent and in general have not caused important clinical problems. Transtracheal oxygen therapy was discontinued in 10 patients before death for various reasons, including infection (2 patients), catheter fracture (1), and surgical emphysema (1). Accumulation of mucus balls has not been a problem. It is concluded that transtracheal oxygen therapy is a safe and acceptable alternative to nasal cannulas in well motivated patients with hypoxaemia due to chronic airflow limitation who are keen to pursue an active life.     

Immunolymphoscintigraphy of pulmonary and mediastinal lymph nodes in dogs: a new approach to lung cancer imaging

Despite improved resolution with new imaging techniques, surgical confirmation of mediastinal lymph node status is often required for reliable staging of patients with non-small cell lung cancer. Recent scintigraphic studies suggest that s.c. administration of radiolabeled antibodies can be more efficient than the i.v. route for targeting regional lymph nodes in animals and humans. To determine if this approach could be applied to the lymphatics of the lung, we injected both specific and irrelevant radiolabeled monoclonal antibodies via a flexible fiberoptic bronchoscope through the mucosa of lobar bronchi in normal dogs. The injected antibodies were expected to drain by way of local lymphatic vessels toward the central lymph nodes, in effect following the same pathway as do cells metastasizing to these nodes during early regional tumor dissemination. To accomplish this, anesthetized dogs were intubated and then coinjected with the two labeled antibodies [600 microCi/100 micrograms (total)] through a fiberoptic bronchoscope. The animals were serially imaged and then autopsied 14-36 h after injection. Individual hilar and carinal nodes contained over 1% of the injected 131I-labeled specific antibody dose and the average selectivity was 2.5:1 with respect to a coinjected irrelevant IgG. Distant organs (mesenteric lymph node, liver, spleen, bone marrow, and lung parenchyma other than the injection site) contained much less radioactivity, and those sites accumulated a greater fraction of the non-specific labeled antibody. The ratio of iodine-131 to iodine-125 counts between hilar/carinal lymph nodes and abdominal lymph nodes ranged from 15:1 to 100:1. These initial studies indicate efficient delivery of antibody to a subset of the regional nodes via pulmonary lymphatics. They suggest the feasibility of this technique which may be of use in the detection and perhaps therapy of human lung cancer metastases in regional lymph nodes.     

Lithium and 5-HT1A receptor sensitivity: a neuroendocrine study in healthy volunteers

The effect of lithium administration (800 mg daily for 7 days) on the neuroendocrine and temperature responses to the 5-HT_1A receptor agonist, gepirone, was studied in eight healthy male volunteers. Gepirone (20 mg orally) significantly increased plasma levels of prolactin, growth hormone, corticotropin and cortisol, and lowered oral temperature. None of these responses was significantly altered by lithium treatment. The results suggest that the ability of short-term lithium treatment to increase 5-HT-mediated neuroendocrine responses in humans is unlikely to be related to changes in the sensitivity of pre- or post-synaptic 5-HT_1A receptors.     

Malignant melanoma over a fifty-year period: a histological evaluation

The incidence of primary cutaneous malignant melanoma is increasing in the developed countries. Cutaneous malignant melanomas diagnosed in our Department over a period of fifty years from 1930 to 1980 were examined to see if there was any change in their histological features. In 1930 and 1955, over 90% of malignant melanomas presented as tumours infiltrating deep into the subepithelial tissue. By 1980, 55% of tumours presented with deeply infiltrating lesions and only 20% occurred at a stage where adequate local excision could provide hope of a cure. There is thus a need for greater awareness among the medical profession and the public if we hope to be able to treat malignant melanomas at an early stage.     

Incomplete excision of the gallbladder during laparoscopic cholecystectomy

Dissection and transection of the cystic duct close to the gallbladder has been advocated as a means of avoiding common bile injury during laparoscopic cholecystectomy (LC). We present three cases in which inadequate identification of the gallbladder—cystic duct junction resulted in incomplete cholecystectomy. In two patients an unsecured gallbladder infundibulum presented as cystic duct leaks and one patient developed recurrent symptomatic cholelithiasis. These cases emphasize the need for complete dissection and visualization of the cystic duct at the gallbladder prior its division and secure ligation during LC.