Citations

1. The short- and long-term effects of oral phosphate supplements were studied in two groups of adult rabbits. 2. In the short-term study, compared with control animals, the bones of phosphate-supplemented rabbits showed a greater degree of porosity, and defects in the tibia created at the beginning of the study were replaced with bone tissue containing many areas of resorption. There was an increase in retention of 85Sr in the hard and soft tissues, particularly in the kidney and thoracic aorta. 3. In the long-term study, a second group of rabbits received a low calcium and phosphate intake during the control period; half of this group were then fed a low dosage of supplemental phosphate while the remaining half remained on the control diet. After a period of 6 months the bones of phosphate-supplemented animals showed increased porosity and there was an increase in 85Sr retention by the kidney compared with the control group. 4. Phosphate supplementation appears to result in secondary hyperparathyroidism and to cause soft-tissue calcification.

DNA viruses are known to be associated with a variety of different cancers. Human papillomaviruses (HPV) are a family of viruses and several of its sub-types are classified as high-risk HPVs as they are found to be associated with the development of a number of different cancers. Almost all cervical cancers appear to be driven by HPV infection and HPV is also found in most cancers of the anus and at least half the cancers of the vulva, penis and vagina, and increasingly found in one sub-type of head and neck cancers namely oropharyngeal squamous cell carcinoma. Our understanding of HPVs role in cancer development comes from extensive studies done on cervical cancer and it has just been assumed that HPV plays an identical role in the development of all other cancers arising in the presence of HPV sequences, although this has not been proven. Most invasive cervical cancers have the HPV genome integrated into one or more sites within the human genome. One powerful tool to examine all the sites of HPV integration in a cancer but that also provides a comprehensive view of genomic alterations in that cancer is the use of next generation sequencing of mate-pair libraries produced from the DNA isolated. We will describe how this powerful technology can provide important information about the genomic organization within an individual cancer genome, and how this has demonstrated that HPVs role in oropharyngeal squamous cell carcinoma is distinct from that in cervical cancer. We will also describe why the sequencing of mate-pair libraries could be a powerful clinical tool for the management of patients with a DNA viral etiology and how this could quickly transform the care of these patients.

1. Five patients with the osteomalacia of chronic renal failure were given 50–100 nmol of 25-hydroxy vitamin D3 intravenously per day for 24–28 days. 2. In all five patients, during administration of 25-hydroxy vitamin D3 there was a substantial rise in the plasma concentration of 25-hydroxy vitamin D from initially abnormally low values. 3. Significant improvement in bone mineralization, intestinal calcium absorption and muscle strength occurred in the three patients with the greatest rise in plasma 25-hydroxy vitamin D.

1. Indomethacin inhibits prostaglandin synthesis and interferes with renin release; these effects were studied in rabbit renovascular hypertension. 2. Ten intravenous inject ons (3 mg day—1 kg—1 after two initial doses of 9 mg/kg) of indomethacin were given daily to ten normal rabbits, ten rabbits with two-kidney Goldblatt hypertension (2KH), and ten rabbits with one-kidney Goldblatt hypertension (1KH). Twelve appropriate control rabbits received diluent phosphate buffer without indomethacin. Plasma renin activity and plasma prostaglandin E2 were measured by radioimmunoassay. 3. In the normal group, indomethacin significantly decreased plasma prostaglandin E2 (1·15 to 0·2 ng/ml, sem 0·2; P < 0·01) and plasma renin activity (20 to 3 ng h—1 ml—1, sem 1, P < 0·01). Plasma creatinine increased slightly but the mean blood pressure was not significantly changed by indomethacin. 4. Six of ten rabbits with 2KH showed results similar to those in the normal rabbits. In four of ten rabbits in which development of 2KH was accompanied by increments in plasma renin activity (18 to 31·5 ng h—1 ml—1, sem 3 and 4 respectively; P < 0·01) and plasma prostaglandin E2 (1·2 to 3·4 ng/ml, sem 0·2 and 0·4 respectively; P < 0·05), treatment with indomethacin produced renal failure (plasma creatinine increasing to 7·6 mg/100 ml), oliguria, malignant hypertension (mean blood pressure, 168 mmHg, sem 7·7) and death within 5 days. 5. In 1KH, indomethacin decreased plasma renin activity and plasma prostaglandin E2, but caused increased mean blood pressure (102 to 121 mmHg, sem 4 and 6 respectively; P < 0·01) and decreased renal function (plasma creatinine 0·9 ± 0·04 to 3·5 ± 1 mg/100 ml, sem 0·04 and 1 respectively; P < 0·01). 6. Aggravation of hypertension was conditioned by pre-existing levels of renal function and, to a lesser extent, by plasma renin activities. 7. These results suggest that prostaglandins exert a protective effect on renal function in renovascular hypertension.

Chemical kinetic data, complemented with scanning electron-microscope observations of the crystalline phase, show that seed crystals of hydroxyapatite have the ability to induce the growth of calcium oxalate monohydrate crystals epitaxially from a metastable supersaturated solution of calcium oxalate. The rate of growth of calcium oxalate crystals is dependent on the surface area of the seed material and follows a second-order rate law. It is suggested that there may be a causal relationship between the occurrence of apatite crystals in the urinary tract and the formation of both ‘pure’ and mixed urinary stones containing calcium oxalate. Under similar experimental conditions, however, seed crystals of calcium oxalate monohydrate appeared unable to induce epitaxially the growth of calcium phosphate crystals from a supersaturated calcium phosphate solution, indicating the absence of an epitaxial relationship between calcium oxalate monohydrate and the initially precipitating calcium phosphate phase(s).

1. Changes in afferent activity in the aortic and sinus nerves with alterations of blood pressure were studied in anaesthetized dogs. Mean aortic blood pressure was changed from 220 to 50 mmHg by using a pressurized reservoir connected to the abdominal aorta. 2. The stimulus-response curve (defined by measuring the mean impulse frequency at various pressures) from both nerves was S-shaped; the curve for the aortic nerve was shifted to the right of the sinus nerve curve. 3. In the dog, the aortic arch baroreceptors act predominantly as an anti-hypertensive mechanism; at lower pressures, the major control occurs through the sinus baroreflex.

1. Hepatic metabolism of renin activity was studied in seven normal dogs, twelve dogs with acute hepatic allograft rejection, five dogs with chronic toxic hepatitis and in seven isolated canine liver preparations. 2. Renin activity was measured by radioimmunoassay in hepatic arterial, portal venous, and hepatic venous plasma (PRA), in bile (BRA) and in perfusate (PsRA). 3. There was a significant gradient of PRA across the normal liver (P < 0.03) and of PsRA across the isolated liver (P < 0.05). 4. There was no significant PRA gradient across the liver of dogs with allograft rejection (acute hepatic necrosis). 5. Dogs with chronic toxic hepatitis showed decreased fractional extraction of PRA but otherwise their data were normal. 6. There was a significant difference between portal venous PRA (8.69 ±1.51 ng ml−1h−1) and hepatic arterial PRA (5.67±1.91 ng ml−1h−1) (P < 0.05). 7. BRA accounted for only 0.04% of hepatic extraction of PRA, suggesting that more important mechanisms for hepatic renin metabolism are binding or destruction of renin by the hepatic tissue.

Summary Objective Epilepsy surgery is the most effective treatment for select patients with drug‐resistant epilepsy. In this article, we aim to provide an accurate understanding of the current epidemiologic characteristics of this intervention, as this knowledge is critical for guiding educational, academic, and resource priorities. Methods We profile the practice of epilepsy surgery between 1991 and 2011 in nine major epilepsy surgery centers in the United States, Germany, and Australia. Clinical, imaging, surgical, and histopathologic data were derived from the surgical databases at various centers. Results Although five of the centers performed their highest number of surgeries for mesial temporal sclerosis ( MTS ) in 1991, and three had their highest number of MTS surgeries in 2001, only one center achieved its peak number of MTS surgeries in 2011. The most productive year for MTS surgeries varied then by center; overall, the nine centers surveyed performed 48% (95% confidence interval [CI] −27.3% to −67.4%) fewer such surgeries in 2011 compared to either 1991 or 2001, whichever was higher. There was a parallel increase in the performance of surgery for nonlesional epilepsy. Further analysis of 5/9 centers showed a yearly increase of 0.6 ± 0.07% in the performance of invasive electroencephalography ( EEG ) without subsequent resections. Overall, although MTS was the main surgical substrate in 1991 and 2001 (proportion of total surgeries in study centers ranging from 33.3% to 70.2%); it occupied only 33.6% of all resections in 2011 in the context of an overall stable total surgical volume. Significance These findings highlight the major aspects of the evolution of epilepsy surgery across the past two decades in a sample of well‐established epilepsy surgery centers, and the critical current challenges of this treatment option in addressing complex epilepsy cases requiring detailed evaluations. Possible causes and implications of these findings are discussed.