Selective modification at the N-terminal region of human growth hormone that shows antagonistic activity

A new analogue of recombinant human growth hormone (hGH), hGH des(1–6,14) was expressed in Escherichia coli, refolded and purified to homogeneity. The mutation decreased the hormone's ability to bind lactogenic and somatogenic receptors through its site 1, and almost completely abolished its ability to bind these receptors through site 2, as evidenced by both binding and gel-filtration experiments. More specifically, the binding to prolactin receptors (PRLRs) from various species or their soluble recombinant extracellular domains (ECDs) was decreased 1.5–4-fold, whereas the binding to hGH receptor (hGHR) was decreased 10–85-fold. These changes caused an almost total loss of hormone agonistic activity in several in vitro bioassays and subsequently, the hGH des(1–6,14) analogue acquired antagonistic properties. This antagonistic activity was dependent upon modification of site 1. In those cases in which the binding was reduced only slightly, e.g. binding to rabbit PRLRs, hGH des(1–6,14) acted as a strong antagonist, whereas in others in which the binding of site 1 was reduced to a higher degree, such as other PRLRs and, in particular, hGHR, the antagonistic activity was correspondingly weaker. Circular dichroism spectra of the analogue suggested that these changes do not result from a decrease in overall -helix content, but rather from minor local structural modifications at the N-terminus.     

Implementation of a successful endovascular surgical program in a non-teaching tertiary-care centre in Ontario.

Endovascular surgical techniques have become an accepted standard of care for high-risk patients with abdominal aortic aneurysms and for certain patients with thoracic aortic pathology and peripheral arterial aneurysms. In Canada, endovascular surgery has been concentrated in tertiary-care academic teaching institutions. As the technology evolves and as expertise advances, the applicability of endovascular techniques will expand. With time, and as the demand for endovascular techniques rises, this expertise will increasingly need to be delivered by dedicated vascular surgical services in nonteaching institutions. The dissemination of endovascular surgical capabilities represent a unique challenge. We report the successful implementation of an endovascular surgical program in a tertiary-care nonteaching institution using a carefully planned preceptorship model. We review our initial 49 cases and discuss 6 factors important to the successful establishment of an endovascular surgical service: education, teamwork, strict selection of patients, use of a single stent-graft manufacturer, industry support and endovascular preceptorship. Our experience may be used as a model by other institutions in Canada.     

Impact of mandibular condyle preservation on patterns of failure in head and neck cancer.

OBJECTIVE: To determine the role of native condyle preservation in local recurrence after segmental mandibulectomy in patients with head and neck squamous cell carcinoma. METHODS: Retrospective chart review with main outcome measuring local control of cancer. RESULTS: Between 1994 and 2003, 72 patients (48 men, 24 women) with an average age of 73.5 years without previous treatment underwent segmental mandibulectomy. Fifty-four cases (n = 54) involved the mandible posterior to the mental foramen and are the subject of this review. In 36 patients, the condyle was preserved and mandibular continuity was restored. In 18 patients, condyle and ramus were resected without mandibular reconstruction. Reconstructive modalities included primary closure (3), split-thickness skin graft (3), pedicle flap (19), and free tissue reconstructions (29). Overall local-regional recurrence rate was 22 percent (12 of 54); no recurrences were identified in patients who underwent condylar resection. Recurrences were observed in patients with mandibular reconstruction by both plate and pedicle flap (5 of 9) or (osteo) myocutaneous free flap (7 of 27). CONCLUSION: Condylar preservation may predispose patients to local recurrence after segmental mandibulectomy. This does not translate into overall reduction in survival.     

Dosimetry associated with exposure to non-ionizing radiation: very low frequency to microwaves

The interpretation of the effects in biological systems exposed to electromagnetic (EM) fields requires knowledge of the internal fields and absorbed energy. The quantification of the specific absorption rate (SAR) is called dosimetry. The SAR given in units of watts per kilogram is a complex function of the source configuration, shape and size of the exposed subjects, orientation of the subject with respect to the source, and the frequency. The average and maximum SAR in the exposed subject may vary over many orders of magnitude for a given exposure level. In order to relate observed biological effects in exposed laboratory animals to safe exposure levels for man, both the fields within the environment and SAR within the exposed tissues must be determined. The environmental fields and the SAR can often be determined from EM theory, but in most cases one must rely on instrumentation such as field survey meters for quantifying the exposure fields and electric field probes, thermocouples, thermistors, fiber optic probes, thermography, and calorimetry for quantifying the SAR in the tissues or equivalent models. A combination of techniques, each valid for a particular model over a particular frequency range, have been used to determine average and peak SARs in humans and animals exposed to plane wave radiation. Though it has been considerably more difficult to quantify these quantities for near field and partial-body exposure conditions, progress is continually being made in this area.     

Lung cancer in Newfoundland, Canada

In this study 1,466 cases of primary lung cancer diagnosed between 1974 and 1983 and reported to the Provincial Tumour Registry, were reviewed. The incidence of lung cancer in Newfoundland has been lower than that in Canada as a whole. The age-adjusted rates for Canadian males and females were 56 and 14 per 100,000 compared to 45 and 7 in Newfoundland. Census division rates showed no association with socioeconomic indicators. The rate in one census division was higher (63 vs 53) most probably because of the higher risk of men who worked in the St. Lawrence fluorspar mines. Although Newfoundland's current smoking rates (39% of men over 15 and 29% of women over 15) are high, this is not reflected in lung cancer rates. Smoking was not widely accepted in rural areas until the time of World War II, and Newfoundland's lower rates may be due to this delay in exposure.     

The Physiology of Gastrocystoplasty: Once a Stomach, Always a Stomach

To determine the physiology of acid secretion after gastrocystoplasty with the body of the stomach we performed a prospective standardized 3-day study in 13 children (median age 12.5 years) who had undergone bladder augmentation/replacement (median postoperative period 2 years). Urinary pH and titratable acid, and serum gastrin levels were measured after gastric distention with a meal and bladder distention with urethral filling at baseline and after medication with a histamine-2 receptor antagonist or an anticholinergic agent. Five children underwent cystoscopy and biopsy of the gastric and native segments of the gastrocystoplasty.

In the fasting state pH was neutral, there was no titratable acid in the urine and serum gastrin level was normal in all cases. After a meal urinary acid secretion and serum gastrin level increased markedly. After each medication half of the patients demonstrated marked inhibition of urinary acid secretion after a meal while response was partial in the remainder. In none of the patients was there significant alteration in the pattern of gastrin secretion. Bladder distention did not result in urinary acid secretion or gastrin secretion. The cystoscopic and histological appearance of the native bladder and stomach segment of the gastrocystoplasty in the 5 patients was normal. We conclude that the gastric body segment used in gastrocystoplasty continues to secrete acid as though it were part of the stomach. The secretion of acid in the urine can be decreased with histamine-2 receptor antagonist or anticholinergic medication.     

Fragmentation process of current laser lithotriptors

Background and Objective: Flashlamp pumped dye (FPDL), Q-switched Nd:YAG, and alexandrite lasers are the most clinically used laser lithotriptors. Although calculi are fragmented by laser induced mechanical stresses for all lithotriptors, different fragment sizes and fragmentation efficiencies have been reported. In this work the effect of the pulse duration and pulse shape on the fragmentation processes is studied. Material and Methods: Fragmentation processes are characterized on model stones and on sensing target fibers. Stone fragmentation and cavitation bubble generation are observed by video flash photography. Shock wave occurrence and strength are monitored with an hydrophone. Results: For the FPDL, stone fragmentation is induced by the collapse of the large cavitation bubble formed. For the Q-switched Nd:YAG, fragmentation is already observed during the laser pulse, at the plasma onset, although further fragmentation can occur at the bubble collapse. For pulse durations corresponding to the alexandrite, an intermediate fragmentation regime is observed. Conclusion: For the first time the physical basis of the observed differences in the fragmentation efficiencies of current laser lithotriptors is described. For nanosecond durations the fragmentation processes are governed by plasma induced shock waves. On the contrary, for microsecond durations fragmentation is governed by cavitation. The high fragmentation efficiency of microsecond lasers is due to a high laser energy transfer into cavitation. © 1995 Wiley-Liss, Inc.     

The depressing effect of tetracaine and ryanodine on the slow outward current correlated with that of contraction in voltage-clamped frog muscle fibres

The effects of tetracaine (10–50 M) and ryanodine (0.1–10 M) were tested on the slow outward K⁺ current (I _so) and the mechanical tension of isolated frog muscle fibres in a voltage-clamp device (double mannitol-gap) connected to a mechanoelectric transducer. In the concentration range tested, both drugs induced a simultaneous inhibition of tension and current. In all cases the effect on tension was twice that on current. The tetracaine-induced current and tension blocks were fully reversible and dose-dependent. In contrast the ryanodine effects on current and tension were not reversible and did not exhibit a dose dependence except for the delay before the onset of the response, which was shortened when the concentration was raised. Linear regression analysis of the time-dependent and dose-dependent effects of both drugs indicated a strong correlation between the decreases in tension and current. It is concluded that the slow outward current is partly under the control of the Ca²⁺ release from sarcoplasmic reticulum during contraction.     

Echography and scintigraphy using technetium 99m pyrophosphate in the diagnosis of cardiac amyloidosis

The diagnosis of amyloid cardiomyopathy was only based, until the last few years, on the results of invasive techniques. It seems presently that the combined contribution of cardiac sonography and scintigraphy using technetium 99m pyrophosphate, makes, most of the time, this diagnosis possible without need for additional examinations. This notion is illustrated by a typical case-report and data from the literature. Demonstration on the cardiac sonogram of a thickening of the walls-while the context and especially the electrocardiogram are not in favor of a left ventricular hypertrophy--associated with a very particular "hyperechoing" aspect and an abnormal fixation on the scintigram, may be considered specific of this disease.