Properties of parathyroid hormone receptors on circulating bovine lymphocytes

Binding of parathyroid hormone (PTH) to circulating bovine lymphocytes was studied using, as the radioligand, a synthetic sulfur-free analog of bovine PTH, [Nle8,Nle18,Tyr34]bPTH-(1-34)amide, which was labeled to high specific activity with 125I and was purified by reverse-phase high-performance liquid chromatography. Binding of PTH to lymphocytes satisfies several criteria indicative of a specific interaction between the hormone and its receptor. Specific binding is saturable at 3.3 fmoles of radioligand bound per 10(7) cells, occurs more rapidly at 37 degrees C than at lower temperatures, and reaches equilibrium within 2 hr at 15 degrees C. Inhibition of specific binding occurs with intact PTH, with biologically active PTH analog or fragment, and with synthetic PTH antagonists, but not with biologically inactive PTH fragments, or peptide hormones unrelated to PTH antagonists, but not with biologically inactive PTH fragments, or peptide hormones receptors on lymphocytes and those previously reported with receptors in canine renal membranes, and on rat osteosarcoma cells. The dissociation constant (Kd) is approximately 10(-9) M, as calculated from the association and dissociation rate constants. This correlates very closely both with the apparent Kd, as estimated from Scatchard analysis of radioligand saturation and competition studies, and with previously reported Kd of PTH receptors in canine renal membranes and on intact rat osteosarcoma and opossum kidney cells. In addition, the relative binding affinity of intact hormone and a synthetic PTH agonist to to receptors on lymphocytes correlates closely with the relative biologic potency of these peptides in stimulating adenylate cyclase in membranes from these cells.(ABSTRACT TRUNCATED AT 250 WORDS)     

Oral contraceptives, reproductive factors and p53 gene expression in colorectal cancer

Protective effects of oral contraceptives and high parity on the development of colorectal cancer have been hypothesized. However, the epidemiological data are inconsistent. This inconsistency may be due in part to the biological heterogeneity of colorectal tumors. A recent investigation of hepatocellular carcinoma demonstrated an association between lack of p53 expression and oral contraceptive use. We investigated the relationship between oral contraceptive use and other reproductive factors with p53 over-expression in 64 post-menopausal women, 45-86 years of age, with non-familial colorectal adenocarcinoma. Fifty per cent (32/64) of colorectal tumors displayed nuclear over- expression of p53 protein. Women with a history of oral contraceptive use were significantly less likely to have p53 positive (+) tumors than women who never used oral contraceptives (P = 0.02). In contrast, tumors from women who had never been pregnant were more likely to be p53 + compared to tumors from parous women (P = 0.10). These data suggest that oral contraceptive use and pregnancy are associated with a p53 independent pathway in the development of colorectal cancer.      

A comparison of ketorolac tromethamine/oxycodone versus patient-controlled analgesia with morphine in anterior cruciate ligament reconstruction patients

Effective postoperative analgesia with minimal side effects remains an important goal in enabling increasingly complex surgical procedures to be performed on an outpatient basis. In this study, we examined the efficacy of postoperative analgesia in 90 patients undergoing anterior cruciate ligament reconstruction using a patellar tendon autograft, with a 24-hour hospital stay. Patients were randomized to receive either intramuscular ketorolac supplemented by oral oxycodone, or intravenous morphine via patient-controlled analgesia (PCA) device, for postoperative analgesia. Patients were monitored for 2 hours in the recovery room, then every 4 hours until discharge, for the presence of complications of nausea, vomiting, urinary retention, pruritus, and dizziness. Pain was assessed using a visual analog scale (VAS) on the morning of postoperative day one. All patients were discharged by 24 hours after surgery. Ten (20%) of the patients receiving ketorolac/oxycodone versus 31 (79%) of those receiving PCA morphine experienced postoperative complications (P < .05). Postoperative nausea, vomiting, and urinary retention were each significantly more common in the PCA morphine group (P < .05). The incidence of pruritus and dizziness was low overall. There was no significant difference between groups in the severity of postoperative pain as assessed using a VAS. We conclude that ketorolac/oxycodone may provide comparable analgesia with fewer undesirable side effects than PCA morphine in patients undergoing anterior cruciate ligament reconstruction. Patients receiving ketorolac/oxymorphone may have a better quality recovery and more rapid discharge. (Arthroscopy 1998 Nov-Dec;14(8):816-9.)     

Argon laser initiated resin photopolymerization for the filling of root canals in human teeth

This work was undertaken to determine if 488 nm light is transmitted through dentin in quantities adequate to polmerize resin located several milimeters from the light source (an optical fiber). The spread of polymerization in a camphorquinone activated resin due to 488 nm light emanating from an opaque plastic canal was compared with light emanating from a canal of the same diameter in tooth dentin. Results indicated that irradiation of a resin-filled chamber via an opaque canal generated a series of ellipsoidal forms, while irradiation via a root canal generated bullet-shaped forms of much larger volume and weight. The base of these bullet-shaped forms was flat against the dentin-resin interface and surrounded the canal. These results indicated that 488 nm argon laser light was transmitted through dentin and could act to polymerize resin at a distance of several millimeters from the canal. Further experiments verified that resin in lateral canals of tooth roots was readily polymerized by 488 nm light applied at low power levels (50 mW). These experiments demonstrate the effectiveness of the argon laser in polymerizing light activated dental resins located within or adjacent to tooth dentin at distances up to several milimeters from the fiberoptic terminus. The flexibility and control that these procedures make possible in the obturation of root canals may lead to substantial improvements in endodontic therapy.     

Long lasting excitability changes in human peripheral nerve

When pairs of equal but submaximal electrical stimuli are delivered to a peripheral nerve, the second stimulus does not always excite the same number of fibers as the first. The number of fibers responding to the second stimulus depends on the interstimulus interval; the refractory period, a well-defined period of hypoexcitability, is followed by longer lasting and less well-characterized periods of hyper- and hypoexcitability. These cycles last at least 200 ms after the initial stimulus. We have carefully studied these cycles of excitability in human peripheral nerve in 12 normal subjects. The magnitude of excitability changes were found to be much greater in motor fibers than in mixed nerve; under some conditions, the motor response was reduced by more than 80% at interstimulus intervals of 40 ms, while the mixed nerve response never varied by more than 20%. In addition, the amplitude of the excitability changes varied as a function of the stimulus strength, so that stimuli that were near threshold or evoked near maximal responses were associated with smaller excitability changes than stimuli evoking midrange responses. Given that the excitability fluctuations are of large magnitude and occur at interresponse intervals easily achieved during physiological firing, it is suggested that they may be important modifiers of firing rate under experimental or physiological conditions. © 1994 John Wiley & Sons, Inc.     

Intra-oral salivary gland tumours in the West Midlands.

Intra-oral salivary gland tumours reported from the West Midlands over the years 1975-88 were examined as to a number of epidemiological variables; the question as to their increasing incidence was also addressed. The findings were largely in agreement with those of most previous authors in that most of the tumours occurred in the palate, but whereas most of these were benign, a large proportion of those in other sites were malignant. However, firm conclusions are difficult to draw since there is much disagreement over reporting criteria. An international workshop and comprehensive tumour registries are required in order to determine more accurate data and conclusions. Similar cooperation is necessary in order to substantiate or refute the suggestion that the incidence of salivary gland tumours is increasing.