A five-year prospective follow-up of women with non-obstructive pyelonephritic renal scarring

Fifty women with pyelonephritic renal scarring were prospectively followed for five years and the changes in renal function were related to blood pressure control, plasma renin activity, urinary albumin excretion and the incidence of urinary tract infections (UTI). Five patients (10%) developed end stage renal disease. All these patients had bilateral disease, proteinuria and anti-hypertensive treatment at presentation. The mean +/- SD glomerular filtration rate (GFR) of all patients with renal scarring was 74 +/- 27 ml/min x 1.73 m2 at presentation which was significantly lower than the GFR in 55 patients with a recent episode of acute pyelonephritis (p less than 0.001) and 10 healthy controls (p less than 0.001). GFR and age corrected GFR decreased significantly during follow-up (p less than 0.001) and p less than 0.02 respectively). The decrease in GFR was significantly higher in patients with bilateral scarring, in patients on blood pressure treatment and in patients with an episode of symptomatic UTI during follow-up. Eight patients (16%) had antihypertensive treatment at presentation and another 11 patients (26%), of whom 10 had bilateral scarring, developed hypertension (greater than 140/90 mmHg) during follow-up. Seventy-five per cent of all patients had symptomatic UTI and 40% had an episode of acute pyelonephritis during follow-up. In conclusion, patients with pyelonephritic scarring have a high incidence of UTI and are at high risk of developing renal failure and hypertension. It is essential that recurrent episodes of symptomatic UTI are treated promptly and that blood pressure is monitored carefully in these patients.     

A noninvasive, in vivo model for studying strain adaptive bone modeling

We present a noninvasive, in vivo model for strain application in the tibiae of rats. The hind limb of each animal was placed into a device that applied four point bending to the tibia. Bending was applied in the medial-lateral direction causing compression on the lateral surface of the tibia and tension on the anteromedial surface. The peak strain magnitudes were estimated to be between 1600 and 3500 mu strain. In this pilot work, data were collected from 12 rats. The rats received either one cycle per day, four cycles per day, 12 cycles per day, 36 cycles per day, or 108 cycles per day of bending. The experimental (right) tibiae from all of the rats showed new bone formation after 12 days. The control (left) tibiae showed no new bone formation over this period. A better organized, dense bony reaction occurred in regions of lesser strains than in regions of higher strains, where there was a large accumulation of bone easily identified as woven. The organization and density of the newly formed bone appeared to be inversely related to the peak strains in the region. After 40 days of daily loading, the new bone area appeared to be more compact and better mineralized. However, bone formation was still occurring after 40 days. The results of this study suggest that woven bone formation occurred due to the bending stimulus and not due to pathology.     

Effect of intraoperative aprotinin administration on postoperative bleeding in patients undergoing cardiopulmonary bypass operation.

To study the hemostyptic effect of aprotinin (Trasylol) in patients undergoing extracorporeal circulation for coronary artery bypass operations, we randomized 12 of 24 patients to receive aprotinin in high dosage (about 800 mg) during extracorporeal circulation. From the resulting two groups each, one patient was excluded from the study because of postoperative myocardial infarction (control group) and surgical hemorrhage (aprotinin group) leading to a second operation. Although heparin was used for anticoagulation in all 22 patients, all had a marked increase in plasma levels of thrombin-antithrombin III complexes during extracorporeal circulation, indicating an intravasal activation of coagulation. By monitoring the plasma levels of fibrin degradation products in patients without aprotinin therapy, we recorded a concomitant hyperfibrinolysis significantly less pronounced in patients receiving aprotinin (p less than 0.005). The mean total postoperative blood loss was lower in patients receiving aprotinin (620 ml) than in control patients (1000 ml; p less than 0.03). The results confirm previous reports of a hemostyptic effect of aprotinin in cardiac operations. This effect is probably due to a prevention of hyperfibrinolysis.     

Familial expansile osteolysis: a morphological, histomorphometric and serological study.

Biopsies from the diseased bones of patients with familial expansile osteolysis (FEO) were examined by light and electron microscopy. Focal concentrations of multinuclear osteoclasts were present, and these contained viral-like microcylindrical inclusions which appeared exclusive to their nuclei. No consistent relationship was found between osteoclast size and the number of osteoclast nuclei containing microcylindrical inclusions. Quantitative histomorphometry showed evidence of increased bone remodelling with high bone cell densities and a decrease of the reversal period in bone remodelling. The lesions contained prominent woven bone and fibrovascular tissue, together with mononuclear cells and adipocytes. Little bone was found in the most radiolucent lesions, which were almost totally occupied by adipocytes and fibrovascular tissue. Serology did not reveal any significant differences between the viral antibody titres of patients and their age- and sex-matched controls. The present study suggests that intranuclear viral-like microcylindrical inclusions of osteoclasts are not a specific feature of Paget's disease, and are found in other disorders of osteoclast function, including pycnodysostosis, osteopetrosis, giant cell tumours, and familial expansile osteolysis.     

A new clinical test in gastroduodenal perforation.

Forty-nine cases of gastroduodenal perforation were subjected to new air insufflation test. The clinical and radiological criteria of air insufflation test were applied to every patient of this study. Forty-seven cases (95.9%) were positive to the new test whereas 2 negative cases turned out to be old sealing perforation. The new test is highly useful in preoperative detection of site of perforation in perforative peritonitis.     

Prokinetic benzamides stimulate peristaltic activity in the isolated guinea pig ileum by activation of 5-HT4 receptors.

Substituted benzamides such as metoclopramide, cisapride, zacopride, renzapride or BRL 20627, stimulate intestinal motility in various species. As they are antagonists at 5-HT3 and agonists at 5-HT4 receptors and as both mechanisms could potentially contribute to their gastrointestinal prokinetic effect, the underlying mechanism is unclear. To clarify this, the effect of some substituted benzamides on gut motility was investigated in the isolated guinea pig ileum using the Trendelenburg technique, in which pressure-induced peristaltic contractions are measured. All benzamides stimulated the peristaltic reflex with the rank order of potency: renzapride greater than cisapride greater than BRL 20627 greater than (+/-)-zacopride greater than metoclopramide. ICS 205-930, granisetron and 2-methyl-5-HT did not change the peristaltic response. 5-HT and 5-methoxytryptamine potently mimicked the effect of the benzamides. The effect of 5-HT was not blocked by ICS 205-930 (10(-7) M). These results indicate that the Trendelenburg preparation is suitable for the investigation of intestinal prokinetic effects of the substituted benzamides. Furthermore, the results suggest that the intestinal effect of benzamides results from activation of 5-HT4 receptors rather than from blockade of 5-HT3 receptors.     

Papilliferous keratoameloblastoma

A case of papilliferous keratoameloblastoma is reported which is only the second ever documented. The patient was a 76-yr-old black woman with a large expansile multilocular radiolucency of the body, angle and ramus of the mandible. Histologically the lesion consisted of sheets of cystic follicles filled with necrotic debris and sometimes parakeratin. The vast majority of the follicles were lined by a papilliferous epithelium consisting of large rounded cells with centrally placed nuclei. True papillary projections with cores of connective tissue were also present. The remainder of the follicles were lined by a thin parakeratinising stratified squamous epithelium. Histological features characteristic of ameloblastoma were absent. Final classification of these lesions will have to await the reporting of further cases.     

Measurement of cerebral monoamine oxidase B activity using L-[11C]deprenyl and dynamic positron emission tomography

A tracer kinetic procedure was developed for the measurement of monoamine oxidase type B (MAO-B) activity using L-[11C]deprenyl and positron emission tomography (PET). The kinetic model consisted of two tissue compartments with irreversible binding to the second compartment (three rate constants). In addition, a blood volume component was included. Special attention was given to the accurate measurement of the plasma and whole blood input functions. The method was applied to the measurement of the dose-response curve of a reversible MAO-B inhibitor (Ro 19-6327). From the results, it followed that the rate constant for irreversible binding (k3) appeared to be a better index of MAO-B activity than the net influx constant Ki. Furthermore, regional analysis demonstrated that Ki, but not k3, was flow dependent. This implies that full kinetic analysis is required for an accurate assessment of MAO-B activity.