Search

The origin of embryo implantation in mammals ~148 million years ago was a dramatic shift in reproductive strategy, yet the molecular changes that established mammal implantation are largely unknown. Although progesterone receptor signalling predates the origin of mammals and is highly conserved in, and critical for, successful mammal pregnancy, it alone cannot explain the origin and subsequent diversity of implantation strategies throughout the placental mammal radiation. MiRNAs are known to be flexible and dynamic regulators with a well-established role in the pathophysiology of mammal placenta. We propose that a dynamic core microRNA (miRNA) network originated early in placental mammal evolution, responds to conserved mammal pregnancy cues (e.g. progesterone), and facilitates species-specific responses. Here we identify 13 miRNA gene families that arose at the origin of placental mammals and were subsequently retained in all descendent lineages. The expression of these miRNAs in response to early pregnancy molecules is regulated in a species-specific manner in endometrial epithelia of species with extreme implantation strategies (i.e. bovine and human). Furthermore, this set of miRNAs preferentially target proteins under positive selective pressure on the ancestral eutherian lineage. Discovery of this core embryo implantation toolkit and specifically adapted proteins helps explain the origin and evolution of implantation in mammals., (© 2023. The Author(s).)

Artificial intelligence is poised to revolutionize the field of medicine, however significant questions must be answered prior to its implementation on a regular basis. Many artificial intelligence algorithms remain limited by isolated datasets which may cause selection bias and truncated learning for the program. While a central database may solve this issue, several barriers such as security, patient consent, and management structure prevent this from being implemented. An additional barrier to daily use is device approval by the Food and Drug Administration. In order for this to occur, clinical studies must address new endpoints, including and beyond the traditional bio- and medical statistics. These must showcase artificial intelligence's benefit and answer key questions, including challenges posed in the field of medical ethics., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose of Review: Barrett's esophagus is the premalignant condition for esophageal cancer and the diagnosis of esophageal adenocarcinoma on index endoscopy is increasing. Many advanced endoscopic techniques are available and aim to identify Barrett's esophagus-associated neoplasia earlier, thereby preventing progression into malignancy., Recent Findings: It is well established adherence to Seattle protocol increases dysplasia detection but leaves large portions of mucosa unsampled. Recent attention has been given to wide-area transepithelial sampling as an additional means of biopsy and shows increased dysplasia detection rates. Many endoscopic techniques aim to increase the success of diagnosis of Barrett's esophagus-associated neoplasia, including probe confocal endomicroscopy, volumetric laser endomicroscopy, and virtual chromoendoscopy. Interestingly, volumetric laser endomicroscopy may also be useful in delineating margins during endoscopic mucosal resection, leading to both diagnostic and therapeutic applications., Summary: Advanced endoscopic techniques are available to increase detection of Barrett's esophagus-associated neoplasia; however, these remain localized to academic centers of excellence. With recent advancements in both sampling techniques and the potential application of imaging to therapeutics, these techniques are becoming more accessible to community endoscopists.

Colorectal cancer, the second most common type of cancer and cause of cancer-related deaths in the United States, can largely be prevented by screening. The 2 most used methods in the United States are colonoscopy and fecal immunochemical testing (FIT). FIT is noninvasive but must be done yearly for optimal performance and, if positive, must be followed by colonoscopy. Colonoscopy is invasive, operator-dependent, and more expensive, but it can detect and remove polyps during the same procedure. The choice of test depends on patient preference, family history, and the likelihood of compliance., (Copyright © 2019 Cleveland Clinic.)

Background and Purpose: We used computer modeling to investigate the influence of physicochemical stone risk factors on urinary supersaturation (SS) of calcium oxalate (CaOx) in patients with severe hyperoxaluria, relative hypocalciuria, hypocitraturia, and CaOx nephrolithiasis after extensive small bowel resection, usually performed for Crohn's disease. We also simulated different treatment strategies, including oral calcium supplements and citrate, in such patients., Materials and Methods: A baseline urine model was derived by consolidating data acquired by ourselves with those from another patient cohort. Calcium and oxalate excretions in this model were altered to obtain an extreme case. For comparison, additional models were based on published urine data from normal subjects (N) and idiopathic CaOx stone formers (SF). The Joint Expert Speciation System was used to simulate different urine situations based on reported compositional values., Results: [Ca(2+)][Ox(2-)] ionic concentration products and SS(CaOx) are substantially higher in enteric hyperoxaluric patients than in N and SF, despite their relatively lower calcium excretions. Molar Ca:Ox ratios are substantially lower in enteric hyperoxalurics than in N and SF. Oral calcium supplements can reduce SS(CaOx), but monitoring is required to avoid exceeding a safe dosing threshold. A simple calculation can alert the clinician that this threshold is being approached or even exceeded. Increasing urinary pH and citrate decreases SS(CaOx) but not to the same extent as decreasing Ox excretion., Conclusions: Calcium supplements can help reduce stone risk in patients with severe enteric hyperoxaluria, but initial efforts should be directed toward reducing urinary oxalate by reducing dietary oxalate. Citrate therapy that increases both urine pH and urinary citrate provides an additional therapeutic benefit.

We report a 55-year-old woman who suffered atypical subtrochanteric femoral fractures (ASFFs) after 4 years of exposure to alendronate and then zolendronate given for "osteoporosis." Before alendronate treatment, she had low bone mineral density. After several months of therapy, metatarsal stress fractures began. Bisphosphonate (BP) administration was stopped following the ASFFs, and the adult form of hypophosphatasia (HPP) was diagnosed from low serum alkaline phosphatase (ALP) activity, high endogenous levels of two natural substrates for the "tissue-nonspecific" isoenzyme of ALP (TNSALP), and a heterozygous mutation within the gene that encodes this enzyme. Experience with other HPP families showed that her mutation (Arg71His) with a second defective TNSALP allele can cause severe HPP in infancy, and when heterozygous can cause mild HPP featuring premature loss of deciduous teeth in children. Because the skeletal disease of HPP results from extracellular accumulation of the TNSALP substrate inorganic pyrophosphate (PPi) and its inhibitory effect on mineralization, perhaps HPP patients or carriers will have adverse effects from BPs. BPs are analogues of PPi and can suppress bone turnover but also deactivate TNSALP. Our report is the first of BP exposure preceding ASFFs in adult HPP. To explore a potential role for TNSALP deactivation in ASFFs, mutation analysis of TNSALP should be studied in a cohort of these patients. Meanwhile, clinicians must suspect HPP when clinical or laboratory clues include premature loss of primary dentition, pseudofractures or recurrent poorly healing metatarsal stress fractures, a family history suggestive of HPP, or low serum ALP activity. If HPP is documented, BP treatment might be avoided. To establish the diagnosis of HPP, assays for two natural substrates for TNSALP and TNSALP mutation analysis are available in commercial laboratories. With positive findings, radiological or bone biopsy evidence of acquired osteomalacia would indicate the adult form of this inborn-error-of-metabolism., (Copyright © 2012 American Society for Bone and Mineral Research.)

A risk index which would reliably predict the likelihood of stone recurrence in the patient with renal calculi would help the clinician to select appropriate preventative therapy. However, none of the indices developed to date combines easy applicability in usual clinical settings with sufficient predictive power to be useful to the clinician in making treatment decisions.

Purpose: Caffeine increases urinary calcium (ca) excretion in nonstone formers. We designed a study to determine the effect of caffeine consumption on urinary composition in stone formers., Materials and Methods: A total of 39 normocalcemic patients with calcium stones consumed caffeine (6 mg/kg lean body mass) after 14 hours of fasting. Urinary composition was compared 2 hours before and 2 hours after caffeine consumption. Control subjects included 9 nonstone formers studied contemporaneously with patients plus data from 39 nonstone formers from previous studies matched to each patient by level of fasting calcium/creatinine (Cr), gender and age., Results: Caffeine increased urinary Ca/Cr, magnesium/Cr, citrate/Cr and sodium/Cr but not oxalate/Cr in stone formers and controls. The Tiselius stone risk index for calcium oxalate precipitation increased from 2.4 to 3.1 in stone formers and from 1.7 to 2.5 in nonstone formers. Of the 39 stone formers 32 had an increased Tiselius risk index after caffeine. Post-caffeine increases in Ca/Cr and Na/Cr were highly correlated., Conclusions: Caffeine consumption may modestly increase risk of calcium oxalate stone formation.

The use of a rapid prototyping method was utilised to produce a pre-operative solid model of the proximal tibia in a patient with a massive defect of the medial tibial plateau. The solid model was reconstructed from aligned sequential CT images of the knee. This was then used to determine the level of bone resection of the proximal tibia for the optimum placement of the tibial component of a total knee replacement. This technique gives the surgeon both the three-dimensional anatomical information needed to ascertain whether there is adequate bony support after cutting for the prosthesis, as well as a solid model on which to carry out the proposed surgery, before undertaking the procedure on the patient.

Hypercalciuria and hyperoxaluria are important risk factors in the pathogenesis of kidney stones. Urinary glycolate has also been reported to be elevated in patients with renal stones. 1,25-Dihydroxyvitamin D(3), the active metabolite of vitamin D, has been reported to induce hyperoxaluria after either oral or intravenous administration. 1-alpha-D(3), a synthetic derivative of vitamin D, together with ethylene glycol, has been reported to induce renal stones in experimental rats. We have examined the effect of 1-alpha-vitamin D(3) on urinary oxalate and glycolate excretion. Our results indicate that 1-alpha-D(3), together with ethylene glycol, caused a significant increase in urinary glycolate, without a parallel rise in urinary oxalate excretion, in ethylene glycol-fed rats. This increase in urinary glycolate was due to the synergistic effect of both drugs.

In common with other multigene families, sequence diversity in the hemoglobin genes of cladoceran crustaceans has been heavily impacted by gene conversion events. Because of their structural complexity (six exons, five introns), these genes provide a good opportunity to study the influence of intron length and position on the conversion process. This study surveys the patterns of divergence in variants of one hemoglobin gene (H1) from two closely related species of Daphnia using a PCR-based approach. Although its effects were most pronounced at their 5' ends, intron and exon regions of these genes showed similar exposure to gene conversion, excepting intron 2. This intron, which was the only one with a marked length difference among variants, showed substantial sequence divergence, suggesting that gene conversion was disrupted. These results, together with those on hemoglobin gene families in other organisms, indicate that sequence tracts showing gene conversion are often distributed in a mosaic fashion. The reactivation of gene conversion downstream of a block protected from its effects suggests that there are multiple initiation points, and the distribution of conversion tracts suggests that exon/intron splice sites are important in this regard.

Plastic organic scintillators are often considered 'water equivalent' in megavoltage photon beams as they have similar atomic composition and density to water. Two plastic scintillators are evaluated for their 'water equivalence', using the Burlin cavity theory, in the photon energy range of 200 keV to 20 MeV. The Burlin theory predicts that the two investigated scintillator materials are likely to be 'water equivalent' in the energy range investigated. The prediction of the Burlin theory for one of these scintillators has been confirmed by absorbed dose measurements in bremsstrahlung beams between 13 and 19 MeV.

An organic scintillator detector system has been developed for radiotherapy bremsstrahlung dosimetry. The scintillators are connected to photodiodes by light pipes as the photodiodes must be removed and shielded from the incident radiation. The photodiodes see visible and near-visible light emissions from the scintillator as well as Cerenkov and fluorescence radiation that has been generated and trapped in the scintillator and light pipe. The Cerenkov and fluorescence radiation limits the accuracy of the dosimeter. This work examines a range of methods for diminishing the signal contribution of Cerenkov and fluorescence radiation while optimizing the scintillator signal. Three methods of achieving these goals have been used. They are: reflective coatings on the scintillator, long-wavelength-emitting scintillators used in conjunction with the photodiode, and absorptive filters placed between the light guide and photodiode. The contribution of the Cerenkov radiation to the light seen by the photodiode has been modelled and the model predictions have been tested using bremsstrahlung beams of peak energy between 13 and 20 MV, showing agreement with measurement.

Abnormalities of bone metabolism and osteopenia (which may be progressive) are features of idiopathic calcium stone disease. This abnormal bone metabolism may be mediated by increased levels of, or responsiveness to, calcitriol or cytokines, including interleukin-1. Bone resorption may be reduced experimentally with bisphosphonates, but for clinical management an appropriate adjustment of dietary calcium intake may be the method of choice to ameliorate bone loss.

1. Until recently studies of intestinal aluminium absorption used pharmacological amounts of stable 27Al. 2. To examine the intestinal absorption of trace amounts of different chemical compounds of aluminium, in the present study we have employed the long half-life isotope of aluminium, 26Al, and accelerator mass spectrometry. Trace amounts of 26Al (2.7-12.1 ng) as the hydroxide, citrate, citrate plus 1 mmol/kg sodium citrate, or maltolate respectively, were administered to four groups of rats (n = 9 per group) by gavage. Blood and urine samples were collected for 5 h and the 26Al content (as a percentage of the administered dose) determined by accelerator mass spectrometry. 3. The 5 h urinary 26Al excretion amounted to 0.1 +/- 0.02, 0.7 +/- 0.2, 5.1 +/- 1.5 and 0.1 +/- 0.1% of administered dose in the four groups respectively. There was a strong positive correlation between peak plasma 26Al (r = 0.98) and urinary 26Al excretion in individual animals (P < 0.001). 4. We conclude that the fractional intestinal absorption of trace oral doses of aluminium hydroxide is at least 0.1% (compared with the previous estimate of 0.01% using large 27Al oral loads). Absorption of aluminium citrate given alone is significantly greater (0.7%) and is further increased to 5% by the accompanying sodium citrate, consistent with an enhancing effect of added citrate upon mucosal aluminium permeability. Aluminium maltolate absorption approximates that of aluminium hydroxide (0.1%).

In adult paraplegic subjects one tibialis anterior muscle received daily electrical stimulation for 4 weeks at twice the motor threshold to determine changes of morphological and histochemical profiles (this paper) and of contractile properties (preceding paper). Bilateral biopsies, obtained 4 weeks before, and immediately after, electrical stimulation, were studied for fibre type proportions, fibre diameters, oxidative capacity, microvasculature and histopathology. Before stimulation the biopsies showed disuse with increased type 2 fibre proportions and decreased oxidative capacity (succinate dehydrogenase (SDH) activity). The effects of two stimulus patterns were compared. Following stimulation SDH activity increased significantly in all stimulated muscles. Inconsistent changes occurred in fibre type proportions, fibre diameters, capillary density and capillary/fibre ratios. Both stimulus patterns evoked similar results. In five/seven subjects subsarcolemmal vacuolation was observed. Electrical stimulation for 4 weeks at only twice motor threshold improves oxidative capacity, but different stimulus parameters are probably needed for significant fibre type conversion.

In adult paraplegic subjects one tibialis anterior muscle received daily electrical stimulation for 4 weeks at twice motor threshold to determine changes of its contractile properties (this paper) and its morphological and histochemical profiles (following paper). Force, speed of contraction and fatigue resistance were assessed by percutaneous electrical stimulation of the muscle with torque measured about the ankle. Comparative contractile tests were performed on 51 normal adult subjects and new parameters for force measurement proposed, particularly where maximum voluntary contraction cannot be obtained. In paraplegic subjects before stimulation the tibialis anterior muscle showed evidence of disuse with decreased force, faster contraction and relaxation, and reduced fatigue resistance. The effects of two stimulus patterns were compared: 10 Hz, and 10 Hz with 100 Hz bursts. After stimulation contraction was slower, fatigue resistance increased and there was a tendency for force to increase. No differences occurred using the different stimulus patterns. Four weeks later fatigue resistance was partially maintained, while speed of contraction reverted to pre-stimulus levels.

Magnesium is an essential cation, involved in many enzymatic reactions, as a cofactor to adenosine triphosphatases. It is critical in energy-requiring metabolic processes, as well as protein synthesis and anaerobic phosphorylation. Serum Mg concentration is maintained within a narrow range by the kidney and small intestine since under conditions of Mg deprivation both organs increase their fractional absorption of Mg. If Mg depletion continues, the bone store contributes by exchanging part of its content with extracellular fluid (ECF). The serum Mg can be normal in the presence of intracellular Mg depletion, and the occurrence of a low level usually indicates significant Mg deficiency. Hypomagnesemia is frequently encountered in hospitalized patients and is seen most often in patients admitted to intensive care units. The detection of Mg deficiency can be increased by measuring Mg concentration in the urine or using the parenteral Mg load test. Hypomagnesemia may arise from various disorders of the gastrointestinal tract, conditions affecting Mg renal handling, or cellular redistribution of Mg. The gastrointestinal causes include the following: protein-calorie malnutrition, the intravenous administration of Mg-free fluids and total parenteral nutrition, chronic watery diarrhea and steatorrhea, short bowel syndrome, bowel fistula, continuous nasogastric suctioning, and, rarely, primary familial Mg malabsorption. The renal causes include Bartter's and Gitelman's syndrome, post obstructive diuresis, post acute tubular necrosis, renal transplantation, and interstitial nephropathy. Many therapeutic agents cause renal Mg wasting and subsequent deficiency. These include loop and thiazide diuretics, aminoglycosides, cisplatin, pentamidine, and foscarnet. Magnesium deficiency is seen frequently in alcoholics and diabetic patients, in whom a combination of factors contributes to its pathogenesis. Hypomagnesemia is known to produce a wide variety of clinical presentations, including neuromuscular irritability, cardiac arrhythmias, and increased sensitivity to digoxin. Refractory hypokalemia and hypocalcemia can be caused by concomitant hypomagnesemia and can be corrected with Mg therapy. The dose and route of administration of Mg in the treatment of hypomagnesemia is dictated by the clinical presentation, the degree of Mg deficiency, and the renal function.

A trace quantity of 26aluminum (26Al) was administered intravenously to 1 normal and 1 uremic rat. After a 3-week period, the animals were sacrificed and samples of bone, muscle, kidney, liver, heart, and brain were analyzed for their 26Al content. In the normal and uremic rats, most of the tissue 26Al was found in bone amounting to 0.9% and 2.0%, respectively, of administered dose/g dry weight of tissue. Much smaller amounts of isotope were found in the other tissues in both animals. In the normal rat, the descending order of 26Al content in other tissues was: kidney, 0.2% > liver, 0.06% > heart, 0.03%, > brain and muscle, 0.02%. In the uremic rat, the same order of tissue 26Al content was found with kidney, 0.37% > liver, 0.06% > heart, 0.02% > brain and muscle, 0.01% per g dry weight of tissue. When expressed per g wet weight of tissue in the 2 animals, a similar order of tissue 26Al content was found. In comparing the amount of 26Al in the bone of the 2 rats, the uremic animal was found to have more than twice that found in the bone of the normal rat when expressed either per g dry or wet weight of bone. However, 26Al content of other tissues was similar in the 2 animals. This suggests that uremic bone may have a greater affinity for aluminum than normal bone, but kidney, liver, brain, heart, and muscle appear to behave similarly in uremic and normal rats in regard to incorporation of a single trace dose of isotope in the 3-week time frame of the present study.

We report the case of a 52-year-old male patient with recurrent thrombosis from 'primary antiphospholipid syndrome' who developed renal microangiopathy. Despite anticoagulant therapy with coumadin, serum creatinine progressively increased from 398 to 592 mumol/l and platelets decreased to 43,000. The patient responded to high-dose methylprednisolone and aspirin and the renal function improved. A review of the literature disclosed 4 other cases of association between primary antiphospholipid syndrome and renal microangiopathy. The clinical characteristics of these cases are discussed.

Enteric hyperoxaluria complicates extensive disease or resection of the small intestine in the presence of an intact colon, and is associated with calcium oxalate nephrolithiasis. In addition to hyperoxaluria these patients have a low urine volume, low urinary ionic strength and hypocitraturia. Many forms of treatment have been recommended, but none has been subjected to a prospective clinical trial. Mild idiopathic hyperoxaluria is reported in 8-50% of idiopathic calcium oxalate stoneformers. Several pathophysiological mechanisms have been proposed, including low dietary calcium and possible oxalate transport defects in the gut and/or the kidney. Mild hyperoxaluria, or a high oxalate:calcium ratio in the urine, may be particularly important risk factors for calcium oxalate stone formation; an approach to the correction of these abnormalities is proposed.

Dietary restriction of oxalate intake has been used as therapy to reduce the risk of recurrence of calcium oxalate kidney stones. Although urinary oxalate is derived predominantly from endogenous synthesis, it may also be affected by dietary intake of oxalate and calcium. The risk of increasing urinary oxalate excretion by excessive consumption of dietary oxalate is greatest in individuals with a high rate of oxalate absorption, both with and without overt intestinal disease. Although oxalate-rich foods enhanced excretion of urinary oxalate in normal volunteers, the increase was not proportional to the oxalate content of the food. Only eight foods--spinach, rhubarb, beets, nuts, chocolate, tea, wheat bran, and strawberries--caused a significant increase in urinary oxalate excretion. Restriction of dietary calcium enhances oxalate absorption and excretion, whereas an increase in calcium intake may reduce urinary oxalate excretion by binding more oxalate in the gut. This review of the literature indicates that initial dietary therapy for stone-forming individuals can be limited to the restriction of foods definitely shown to increase urinary oxalate. The effects of oxalate-restricted diets on urinary oxalate should be evaluated by means of laboratory analyses of urine composition. Subsequent long-term therapy can be recommended if beneficial results are obtained from oxalate restriction at an appropriate calcium intake.

Plasma osmolality normally decreases in early pregnancy, reaching a minimum at approximately 10 weeks and remaining depressed until term. This is associated with a mean decrease of 4 mEq/L in the plasma sodium level, and with an altered threshold for arginine vasopressin (AVP) release and for thirst. We describe a patient who developed more severe hyponatremia (120 mEq/L), which accompanied the development of hypertension and edema at 37 weeks in her fourth pregnancy. Hyponatremia and hypo-osmolality were associated with marked elevation of the plasma AVP level. The hyponatremia and elevated AVP level resolved after the delivery of the infant. To our knowledge, this is the first reported example of transient inappropriate antidiuretic hormone secretion (SIADH) associated with pregnancy.

Cisplatin is an antineoplastic agent. Several nephrotoxic effects are associated with its use including chronic and acute renal failure, renal magnesium wasting, and polyuria. We have investigated polyuria in groups of rats treated with cisplatin at doses of 2.5 and 5 mg/kg body weight given once weekly for 3 weeks to determine possible mechanisms of this impairment. After cisplatin administration, glomerular filtration rate was reduced and significant increases in sodium and water loss were also seen. These changes were associated with decreases in urinary cAMP. Inner medullary collecting duct (IMCD) cells were removed from these animals and were stimulated with graded doses of vasopressin. Cells from cisplatin-treated rats showed an impaired response in cAMP generation to vasopressin stimulation as compared to cells from normal animals. To determine more precisely the site of impairment, the adenylate cyclase complex of the IMCD cells was further studied with forskolin and NaF. Forskolin was used to probe the catalytic unit activating adenylate cyclase, and NaF the guanine nucleotide regulatory protein (G protein). In response to forskolin, cells from cisplatin-treated rats and normal rats responded similarly in generating cAMP. However, following NaF, the cAMP response was blunted in the cells from the cisplatin rats. These results suggested that the catalytic unit was not injured by cisplatin (forskolin study) but the G protein was (NaF). In conclusion, the present study suggests that the polyuria seen following cisplatin administration is associated with an end-organ resistance to vasopressin manifested by reduced cAMP generation, secondary in part or whole to a defect at the level of the G protein.

High-performance ion chromatography (HPIC) has been widely used for oxalate analysis and, more recently, for glycolate analysis. We describe a procedure for sample preparation in which the plasma ultrafiltrate is acidified during harvesting with a cation-exchange resin, and the chloride is removed before the ion chromatography, which is performed with a newly developed AS10 column. The same ultrafiltrate sample is analyzed for glycolate. For plasma oxalate, the mean recovery of sample in eluted fractions was 95-96%, and intraassay CV was 6.2-8.1%. The reference interval (mean +/- 2 SD) for men was 0.8-3.2 mumol/L and for women, 1.0-2.6 mumol/L. For urinary oxalate, the reference interval for men was 175-560 mumol/day and for women, 107-432 mumol/day. For plasma glycolate, the mean analytical recovery was 96-98%, and the intra-assay CV was 2.4-6.2%. The reference interval for men was 1.9-7.5 mumol/L and for women, 1.4-7.4 mumol/L. For urinary glycolate, the reference interval for men was 0-1400 mumol/day and for women, 91-1001 mumol/day.

The normal fractional urinary excretion of filtered magnesium is about 5%. In magnesium deficiency in man, the kidneys can normally reduce the 24-hour urinary magnesium excretion to less than 1 mmol (24 mg) via unknown mechanisms, and initially without a fall in plasma magnesium concentration. Renal magnesium wasting may be defined as a urinary excretion greater than 1 mmol/day in the presence of hypomagnesemia (plasma magnesium < 0.7 mmol/l). Congenital renal magnesium wasting occurs in several syndromes including Bartter's syndrome in which it is associated with hypercalciuria, and the defect may be in the thick ascending limb of Henle's loop, and Gitelman's syndrome in which there is hypocalciuria, and the defect may be in the distal convoluted tubule. Other causes of renal magnesium wasting include diabetes mellitus, hypercalcemia and diuretics. Magnesium wasting may also result from various toxicities including those of cis-platinum, in which the biochemical features resemble Gitelman's syndrome, and those of aminoglycosides, pentamidine and cyclosporin. Calcitriol deficiency may also contribute to renal magnesium wasting in some circumstances. Mild hypermagnesemia may occur in familial hypocalciuric hypercalcemia and may reflect abnormal sensitivity of the loop of Henle to calcium and magnesium ions. By contrast, the hypermagnesemia that occurs in chronic renal failure results from the reduced glomerular filtration of magnesium.

The performance of K-edge filters to modify the x-ray spectrum is investigated experimentally in a variety of clinical situations involving bone/soft tissue imaging, with the aim of improving the optimization between image contrast and patient exposure. The results show that simultaneous improvement of contrast and reduction of exposure is possible for a wide range of patient sizes. For conditions of fixed contrast skin exposure reductions of better than 50% and integrated dose reductions of up to 30% have been achieved with tolerable increases in tube load. Rare earth salt solutions were used as an inexpensive alternative source of K-edge filtration, and their performance was found to be in no way inferior to that of expensive metal foils.

Renal tubular function was examined in 5 adult patients aged 18-30 years with Bartter's syndrome associated with renal magnesium wasting and hypocalciuria. In the 3 patients studied during hypotonic saline diuresis, distal tubular fractional chloride reabsorption was lower than that reported in normal subjects. In response to a single intravenous dose of furosemide (40 mg), the increment in the excretion of sodium, chloride, and magnesium was equal to or greater than in normal subjects, while in 2 patients, in response to intravenous chlorothiazide (500 mg), the increment in sodium excretion was less than in normal subjects. Magnesium chloride infusion was undertaken in 2 patients in order to compare magnesium and calcium excretions at similar plasma magnesium levels in patients and in normal subjects. The patients exhibited magnesium wasting only at normal or low plasma magnesium levels, while calcium excretion was reduced in the patients at normal and elevated plasma magnesium levels. We conclude that in these patients the enhancement of renal magnesium reabsorption by hypomagnesemia is defective, and the hypomagnesemia is not the cause of the hypocalciuria. The tubule defect responsible for these abnormalities of magnesium and calcium excretion may be located beyond the side of action of furosemide, in the thiazide-sensitive segment of the distal convoluted tubule.

Twenty patients at the Northern Regional Spinal Injury Unit received carbon fibre implants inserted into the sites of previously closed pressure sores or threatened pressure sores. The most common site was over the ischium, but some have also been inserted at the trochanteric area, the sacral area and also over bony protuberances of the leg. Seven implants from four patients had to be removed because of damage or infection. Sixteen patients with 18 implants have proceeded with no recurrence for a period of 4-8 years.

Kidney stones are common, and recurrences are the rule. At least 90% of patients with kidney stones probably have some identifiable metabolic risk factor. Effective prophylaxis is often available, but with the relatively low rate of recurrence, compliance with the treatment may be a problem. Studies are required to determine the cost-effectiveness of metabolic investigation and prophylactic therapy versus the possible need for repeated treatment by means of extracorporeal lithotripsy, especially in patients having a first calcium oxalate stone.

The advent of accelerator mass spectrometry (AMS) now permits the ultrasensitive detection of extremely long-lived isotopes, including 14C, 26Al, and 41Ca. Until now, tracer studies of aluminum kinetics have not been possible because aluminum has only two isotopes, with half-lives of 6.5 min (29Al) and 7 x 10(5) yr (26Al), neither of which is suitable for conventional studies. In a novel experiment we have employed AMS to study aluminum kinetics in a normal rat and a 5/6-nephrectomized rat over a 3-wk period of intravenous injection of a tracer dose of 26Al. Kinetics were similar in the two animals; approximately 75% of intravenously injected tracer 26Al was excreted in the urine in the first 24 h as was approximately 80% after 3 wk. Renal clearance of 26Al was approximately 0.75 ml.min-1.kg body wt-1 in both rats. The results clearly demonstrate the potential of this technique for isotope tracer studies in animals as well as in humans.

Previous studies in our laboratory have shown that patients with idiopathic hypercalciuria (IH) have low basal atrial natriuretic factor (ANF) levels in the plasma. These depressed ANF levels are associated with a high plasma calcitriol levels. In this study, we have evaluated the effect of acute calcitriol administration on ANF release in the isolated atrium. There was a gradual reduction of ANF release as the dosage of calcitriol increased from 1 ng to 10 ng. Beyond 10 ng, additional suppression of ANF release by calcitriol was not observed. These results indicate that acute calcitriol administration causes a significant decrease in ANF release. To further determine whether this reduction in ANF release is due to changes in plasma calcium, additional studies were conducted to examine the effect of acute changes in perfusate calcium on ANF release by isolated atria. Acute elevation of perfusate calcium caused an increase in ANF release, whereas a reduction significantly decreased the secretory rate. These observations suggest that calcitriol affects ANF release by a mechanism not dependent on changes in plasma calcium.

A group of six patients with hypomagnesemia (serum magnesium less than or equal to 0.5 mmol/L), previously given treatment with cisplatin for ovarian or testicular cancer, received calcitriol at a dose of 0.5 to 1.0 microgram/day for a period of 4 weeks to determine whether treatment with this vitamin D metabolite could improve their hypomagnesemia. In response to treatment, the serum magnesium concentration fell progressively in association with a rise in serum and urinary calcium levels and a decrease in parathyroid hormone level. In a single previous report, active vitamin D metabolites markedly improved renal magnesium wasting. However, in the present study, increases in serum and urinary calcium levels and suppression of parathyroid hormone, factors known to decrease magnesium reabsorption, presumably overwhelmed any direct effect calcitriol may have had to enhance magnesium reabsorption, so that the net effect was a marked exacerbation of the renal magnesium wasting.

Cisplatin (CIS-diamine dichloroplatinum) is a highly nephrotoxic antineoplastic agent which may cause acute renal failure and renal tubular dysfunction. In the present study we have examined the effect of chronic cisplatin administration on sodium-dependent 32P-phosphate and 3H glucose transport by the renal brush border membrane vesicles (BBMV). Our results indicate that both transport mechanisms were significantly reduced at the BBMV following cisplatin therapy due to an increased Km (0.13 +/- 0.09 vs. 0.34 +/- 0.09 mM; p = less than 0.01) without significant change in Vmax (56 +/- 18 vs. 44 +/- 17 pM/mg/s). The results of these studies indicate that cisplatin causes a diffuse renal injury in the proximal segment of the nephron altering both transport mechanisms. Possible mechanisms of cisplatin nephrotoxicity are discussed.

Ionized calcium is a stimulator for the release of several peptide hormones. Atrial natriuretic factor (ANF) is a peptide hormone released from atrial tissue in response to atrial distension or volume expansion. In the present study, we have examined the effect of an oral calcium load in healthy controls and renal stone patients with idiopathic hypercalciuria. Our results demonstrated that ANF release increased in both groups in response to a calcium load. However, idiopathic hypercalciuric patients presented lower basal ANF levels in the presence of high calcitriol levels. The role of calcitriol on ANF release remains to be evaluated.

The effect of the calcium antagonist verapamil, and of thiazide, a well accepted treatment in the prevention of calcium oxalate renal stones, were examined in an experimental renal stone model. Calcium oxalate stones were induced by the synthetic metabolite of vitamin D3, the alpha-OH-vitamin D3 plus ethylene glycol fed rats. A significant decrease in urinary calcium and oxalate was observed following verapamil treatment. Thiazide significantly decreased urinary calcium, but unlike verapamil, did not decrease urinary oxalate. However, no differences in the radiological findings or in the calcium or magnesium content of the kidneys were observed. Although several animal models have been described for the study of calcium oxalate stones, none has yet been proven useful for the evaluation of stone therapy.

Idiopathic calcium stone-formers with hypercalciuria during fasting have significantly lower urinary cyclic AMP levels (nmol/dl of glomerular filtrate) than fasting normocalciuric stone-formers. Female subjects, including both normal subjects and idiopathic calcium stone-formers, have higher urinary cyclic AMP levels than their male counterparts, and this difference is significant when urinary cyclic AMP is expressed in the units mumol/g of creatinine. Expressing urinary cyclic AMP in nmol/dl of glomerular filtrate reduces this difference but does not abolish it. Thus, in comparing urinary cyclic AMP levels in various subgroups of the calcium stone-formers and in normal subjects, both sex differences and the units of urinary cyclic AMP expression must be taken into consideration. The magnitude of the change in urinary cyclic AMP in response to an oral calcium load appears to depend on the antecedent urinary cyclic AMP excretion rate, whereby those individuals (either normal subjects or calcium stone-formers) having the highest urinary cyclic AMP levels demonstrate the greatest fall in urinary cyclic AMP after a calcium load.

The relationship between the applied torque and the load required to pull off the calipers was established on cadavers. Torques of 0.7, 0.8 and 0.9 Newton-metres were applied to a specially adapted skull traction caliper whilst attached to the skull in the normal position when used clinically, and loads were applied in steps of 2 lb up to a maximum of 60 lb. It was found that at a torque of 0.7 Newton-metres, the caliper became detached at the maximum load, but still held during traction at torques above this value. Taking into account the fall in load with time that may occur clinically and the limiting torque for pull-out with a traction load of 60 lb, it is suggested for complete clinical safety that a torque of 0.9 Newton-metres should be applied. An open-ended torque release spanner was set for 0.9 Newton-metres for clinical use such that the compressive load is sufficient to prevent pull-out even in the unlikely event of 60 lb being applied for up to 21 days.

The effects of 1,25(OH)2D3 on the renal handling of calcium (Ca), magnesium (Mg), and phosphate (Pi) in the thyroparathyroidectomized (TPTX) hamster were studied in the presence of exogenous PTH. Clearance experiments were performed in the following groups: acutely TPTX animals (group 1), acute TPTX plus continuous infusion of PTH in low or high doses sufficient to (1) reduce or (2) abolish the hypocalcemic effect of TPTX (groups 2 and 3, respectively), and acute TPTX plus Ca (group 4) or Pi (group 5) infusion. Each group was subdivided into control and experimental subgroups. In all animals an initial control phase was followed by a second phase in which experimental animals received an infusion of 1,25(OH)2D3 (1 U prime + 0.5 U/hr) while control animals received only the ethanol vehicle. GFR and urine flow rate, were not altered significantly in any of the groups. PCa and PMg increased significantly in group 3 only. Group 2 showed an increase in FECa (5.2 +/- 1.4 to 13.2 +/ 2.2%, P less than 0.001) and FEMg (7.3 +/- 1.3 to 17.3 +/- 2.2%, P less than 0.001) in response to 1,25(OH)2D3. Group 3 showed a significant increase in FEMg only (2.2 +/- 0.4 to 5.5 +/- 1.0%, P less than 0.01). The changes in the control groups were not significant. The administration of 1,25(OH)2D3 reduced phosphate excretion only in the presence of PTH. The FEPi decreased from 11.9 +/- 2.1 to 3.6 +/- 0.9% (P less than 0.001) in group 2 and 29.2 +/- 4.0 to 16.5 +/- 2.5% (P less than 0.02) in group 3.(ABSTRACT TRUNCATED AT 250 WORDS)

Twenty-two adult males participated in a 5 week progressive strength training program. One half the subjects received the amino acids L-arginine and L-ornithine and the other half, a placebo. The study used a double blind protocol so that subjects as well as investigators had no knowledge of which substances were being administered. Dosages amounted to 2 grams or 1 gram each of L-arginine and L-ornithine, and 600 mg of calcium and 1 gram of Vitamin C as placebos. These supplements were taken orally for a total of 25 administrations. Following the short term strength program using progressively high intensities, tests were taken for total strength (TS), lean body mass (LBM) and urinary hydroxyproline (UH). The results from ANOVA showed that subjects who were taking the arginine-ornithine combination scored significantly higher in TS and LBM (p less than .05), and significantly lower in UH (p less than .05), than subjects on placebos. It was concluded that arginine and ornithine taken in prescribed doses can, in conjunction with a high intensity strength training program, increase TS and LBM in a relatively short period of time. Arginine and ornithine also aid in recovery from chronic stress by quelling tissue breakdown as evidenced by lower UH levels.

The effect of acute metabolic acid-base changes on renal magnesium transport is not well defined. We have examined renal magnesium handling in three groups of ten acutely thyroparathyroidectomized rats infused with isotonic NaCl (controls), NH4Cl (acidosis), and NaHCO3 (alkalosis). To define the interactions of furosemide with acid-base changes and in an attempt to localize the site of action of acidosis and alkalosis on tubular magnesium transport, the rats were studied in a second phase after administration of a maximal dose of furosemide. Before furosemide, the blood pH was 7.40 in the controls, 7.27 (P less than 0.001) in the acidotic rats, and 7.56 (P less than 0.001) in the alkalotic rats. The filtered magnesium load was not significantly different in the three groups, but fractional excretion of magnesium (FEMg) was 33.7%, 37.4%, and 13.3% in the controls, the acidosis group, and the alkalosis group, respectively. Following furosemide, the blood pH was unchanged in each group, but FEMg increased significantly to 55.4%, 71.1% (P less than 0.01 compared with controls), and 41.4% (P less than 0.01 compared with controls) in the controls, the acidotic rats, and the alkalotic rats, respectively. These data indicate that metabolic alkalosis per se enhances renal magnesium transport, and this effect is also evident after blockade of loop magnesium reabsorption by a maximal dose of furosemide. Acidosis per se does not significantly alter magnesium transport, but an inhibitory effect of acidosis on magnesium reabsorption becomes evident when distal magnesium delivery is greatly increased by furosemide. These interactions suggest that metabolic acid-base changes and furosemide may influence magnesium reabsorption at different tubule sites.(ABSTRACT TRUNCATED AT 250 WORDS)