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Biomedical subjects

R L Hackett

Publications and source records attributed to R L Hackett.

At least 37 records · Page 2Linked to original sources

Effect of magnesium on calcium oxalate urolithiasis.

Previous studies have shown that hypomagnesuria induced by magnesium deficient diet causes calcium oxalate crystal deposition in renal tubules of hyperoxaluric rats and administration of magnesium to these rats results in prevention of calcium oxalate crystallization in their kidneys. Based on these studies magnesium was claimed to be beneficial for calcium oxalate stone patients. However, hypomagnesuria is not a common phenomenon. To better understand the role of magnesium as an inhibitor of calcium oxalate crystallization in urine, we studied the effect of magnesium on calcium oxalate urolithiasis in rats on a regular diet and a hyperoxaluric protocol. Excess magnesium was administered to male rats on regular diet and a lithogenic protocol. Magnesium administration to hyperoxaluric rats did not result in significant changes in urinary excretion of calcium or oxalate or in calcium oxalate relative supersaturation. Urinary excretion of citrate was also not significantly altered. Some animals from both groups, those on magnesium therapy and those not on magnesium therapy had crystals deposited in their renal tubules. We conclude that excess magnesium has no significant effect on calcium oxalate urolithiasis in normomagnesuric conditions.

Animals↗

Retention of calcium oxalate crystals in renal tubules.

Crystal retention within the renal tubules is essential for nephrolithiasis and the development of urinary stone disease. We studied the mechanisms involved in this process by inducing calcium oxalate crystal deposition within the rat renal tubules and examining them using various microscopic techniques. Crystals appeared to be retained either by attachment to the tubular epithelium or by aggregating with other crystals thus becoming large enough to be retained by their collective size.

Animals↗

Prophylactic glutamine protects the intestinal mucosa from radiation injury.

Glutamine may be an essential dietary component, especially for the support of intestinal mucosal growth and function. This study evaluated the effects of a glutamine-enriched elemental diet, administered before whole-abdominal radiation on gut glutamine metabolism, mucosal morphometrics, and bacterial translocation. Rats were randomized to receive a nutritionally complete elemental diet that was glutamine-enriched or glutamine-free for 4 days. The animals were then subjected to a single dose of 1000 cGy x-radiation to the abdomen. After irradiation, all animals received the glutamine-free diet. Four days later the animals underwent laparotomy for sampling of arterial and portal venous blood, culture of mesenteric lymph nodes, and removal of the small intestine for microscopic examination. There was no difference in arterial glutamine or gut glutamine extraction between the two groups, but body weight loss was significantly diminished in the glutamine-fed rats. Rats receiving the glutamine-enriched elemental diet before radiation had a significant increase in jejunal villous number, villous height, and number of metaphase mitoses per crypt. Scanning electron microscopy confirmed the presence of an intact gut epithelium in eight of eight rats receiving prophylactic glutamine compared to one of eight animals in the glutamine-free group. Three of eight rats fed glutamine had culture positive mesenteric lymph nodes compared with five of seven rats receiving the glutamine-free diet. Glutamine exerts a protective effect on the small bowel mucosa by supporting crypt cell proliferation effect on accelerate healing of the acutely radiated bowel.

Animals↗

Membrane-associated crystallization of calcium oxalate in vitro.

Incubation of proximal tubular brush border membrane in a metastable calcium oxalate solution of low supersaturation resulted in the equimolar depletion of calcium and oxalate and the formation of monoclinic calcium oxalate crystals. We propose that membrane fragments from sloughed epithelial cells of the nephron can similarly induce crystallization in urine that is metastable for calcium oxalate.

Animals↗

Cell injury associated calcium oxalate crystalluria.

Renal tubular cell damage, resulting in membranuria, was induced by the administration of subcutaneous gentamicin to male Sprague-Dawley rats. One group of rats received gentamicin only, while a second group was given gentamicin plus ethylene glycol in drinking water at a concentration which increased urine oxalate but alone did not cause calcium oxalate crystalluria. Crystalluria occurred early in the combined treatment groups and persisted for the duration of the experiment. Crystalluria was not present in animals receiving gentamicin or ethylene glycol only. These results suggest that cellular fragments can serve as heterogeneous foci for the nucleation of calcium oxalate crystals.

Animals↗

Urinary enzymes and calcium oxalate urolithiasis.

Male Sprague-Dawley rats were challenged with various hyperoxaluric agents including ammonium oxalate, hydroxy-L-proline, and ethylene glycol. All treatments resulted in increased urinary oxalate. Associated with hyperoxaluria was an increase in urinary levels of renal enzymes, gamma-glutamyl transpeptidase, N-acetyl-beta-glucosaminidase, and alkaline phosphatase. Most of the rats did not demonstrate any significant change in urinary levels of beta-galactosidase. There was a highly significant positive correlation between urinary oxalate and N-acetyl-beta-glucosaminidase.

Acetylglucosaminidase↗

Validation of the smoking habits of a sample of the patient population seen in a pulmonary function laboratory.

From a structured history of 32 current smokers seen in the pulmonary function laboratory of a community hospital, we determined the number of cigarettes they smoked in 24 h. We also asked them to estimate their cigarette butt lengths from a visual model and to collect all cigarette butts over the next 24 h and mail them to us. We counted the butts, individually measured their lengths, and compared these with their previous estimates in order to validate their claims. While in the laboratory, we determined the level of carboxyhemoglobin in the peripheral blood of each patient. Patients tended to estimate the numbers of cigarettes that they smoked in units of five. Light smokers returned more butts and heavy smokers returned fewer butts than the numbers they reported as usually smoking. All patients were able to precisely estimate the average length of their cigarette butts, and they left butts of consistent lengths. There was no association between the numbers of cigarettes smoked and the butt lengths. Carboxyhemoglobin levels were positively associated with the numbers of cigarettes smoked in 24 h and negatively associated with the butt length and the time elapsed since the last cigarette was smoked, but these were not associated with the amount of tar in the cigarettes or with the number of years the person had smoked.

Adult↗

Presence of lipids in urinary stones: results of preliminary studies.

The presence of lipids in urinary stones was determined by histochemical and biochemical methods. When crystals of calcium oxalate, made by mixing calcium chloride and potassium oxalate solutions and sections of human calcium oxalate urinary stones, were exposed to osmium vapors, there was no staining of the pure crystals whereas the stone sections were stained. De-paraffinized sections of demineralized calcium oxalate stones showed positive sudanophilia on staining with Sudan black B. Both these experiments indicate the presence of lipids in calcium oxalate stones. Lipids were extracted from uric acid, struvite, and calcium oxalate stones using standard techniques. Phospholipids were separated by one-dimensional thin layer chromatography. All the stones studied contained lipids. In calcium oxalate stones they accounted for 10.15% of the matrix. Calcium oxalate and struvite stones contained more phospholipids than uric acid stones. Cardiolipin, sphingomyelin, phosphatidyl choline, phosphatidyl inositol, phosphatidyl ethanolamine, phosphatidyl serine, and phosphatidyl glycerol were identified in lipid extracts. Demineralization by ethylenediaminetetra-acetate (EDTA) treatment increased lipid output from calcium oxalate stones by 15.5%.

Calcium Oxalate↗

Extracorporeal shock-wave lithotripsy (ESWL). II. In vivo canine results of blast path treatment of human gallstones.

To evaluate the role of ESWL in vivo for the treatment of human gallstones positioned on the blast path, a canine model was developed to determine the efficacy of stone fragmentation and the subsequent histopathological injury that occurs as a result of this therapeutic technique. Twenty-four 16- to 20-kg mongrel dogs were divided into five groups: I: ESWL without stone, autopsy at 48 hr (N = 6); II: ESWL with stone (mean diameter 16.8 mm, range = 14-19 mm), autopsy at 48 hr (N = 10); III: ESWL without stone, autopsy at 41-46 days (N = 6); IV: ESWL without stone, autopsy immediately after ESWL (N = 1); V: No ESWL or stone, autopsy 2 hr after anesthesia induction (N = 1). A human gallstone (96% cholesterol) was inserted by cholecystotomy (N = 10) in Group II only. All groups (N = 24) had operative placement of a 6.5 Fr accordion catheter into the gallbladder for radiographic visualization. For each blast path treatment, 2000 discharges were delivered at 18-24 kV. Histopathologically, the Group V gallbladder served as a control. Groups I, II, and IV revealed mild subacute injury; dog gallbladders in Group III showed regression of these changes. Total surface area (TSA) of Group II stones increased from a pre-ESWL mean of 6.60 +/- 0.0.84 cm2 to 53.84 +/- 26.8 cm2 post-ESWL (P less than 0.001). Cumulative post-ESWL fragment sizes for particles in less than or equal to 2-, less than or equal to 3-, less than or equal to 5-, less than 10- and greater than or equal to 10-mm categories represented 32.9, 41.6, 49.4, 74.3, and 100% of pretreatment stone weight, respectively. These data indicate that human gallstones can be fractured to a variable degree when treated on the ESWL blast path and that TSA increased significantly. Gallbladder histopathologic changes appear to be reversible by 41-46 days post-ESWL.

Animals↗

In vitro precipitation of calcium oxalate in the presence of whole matrix or lipid components of the urinary stones.

Organic matrix of human calcium oxalate urinary stones was obtained by demineralizing with EDTA. Lipids were extracted from the EDTA-insoluble matrix by chloroform methanol treatment. The whole matrix and its total lipid extract were then incubated in a metastable solution of calcium oxalate and depletion of calcium and oxalate ions from the calcifying solution was determined. Results of our studies described here show that urinary calcium oxalate stone matrix and its total lipid contents were capable of binding calcium and oxalate ions and of catalysing calcium oxalate crystal formation from a metastable calcium oxalate solution.

Calcium Oxalate↗

Primary malignant melanoma of the male urethra.

Primary malignant melanoma of the male urethra is a rare disease, with only 24 cases previously reported in the literature, including 1 black patient. We describe 2 additional patients with primary malignant melanoma of the urethra, one of whom was a black man. The literature is reviewed briefly and treatment recommendations are discussed.

Aged↗

Presence of calcium oxalate crystals in the mammalian thyroid gland.

Birefringent crystals of calcium oxalate have been previously identified in the colloid of human thyroid glands. We found such crystals in 19/20 adult thyroids at autopsy, in 4/20 infants at autopsy, and, using frozen sections, in 19/20 thyroids partially or totally removed at surgery. These crystals were soluble in hydrochloric acid, insoluble in acetic acid, and contained only calcium by energy dispersive X-ray microanalysis, confirming their calcium oxalate character. Similar crystals were found in equine and ovine thyroids.

Birefringence↗

Crystal-matrix relationships in experimentally induced urinary calcium oxalate monohydrate crystals, an ultrastructural study.

Calcium oxalate monohydrate crystalluria was experimentally induced in male rats by administration of ethylene glycol. The crystalluria particles were separated by filtration and studied by scanning and transmission electron microscopy. They were associated with cellular degradation products. Organic material was present both on the surfaces of crystalluria particles as well as within them and was organized in radial striations and concentric laminations. It is proposed that crystal nuclei were formed by heterogeneous nucleation. These nuclei then adsorbed organic material and aggregated. The organic material polymerized resulting in the formation of a crystal-matrix unit which then grew and incorporated more organic material during the crystal growth.

Animals↗

Urolithogenesis of mixed foreign body stones.

Urine of male Sprague-Dawley rats was supersaturated for struvite and often contained struvite crystals. Ethylene glycol administration to these rats resulted in elevation of urinary oxalate and calcium oxalate supersaturation, and induced calcium oxalate crystalluria. Implantation of foreign bodies in their urinary bladders and changing their urinary ambient conditions by administering ethylene glycol for two weeks at two week intervals resulted in the formation of urinary stones of mixed composition containing calcium oxalate and struvite. Crystal-onto-crystal epitaxy did not appear to play any role in the development of these stones.

Animals↗

Role of scanning electron microscopy and x-ray microanalysis in the identification of urinary crystals.

Urinary crystals can be identified by using analytical electron microscopic techniques of scanning electron microscopy and energy dispersive x-ray microanalysis. Crystal habit can be recognised by scanning electron microscopy and their chemical nature by elemental analysis. With a conventional detector the lightest element that can routinely be detected is sodium, but with a windowless or thin window detector even carbon can be detected. Thus almost all the commonly occurring urinary crystals including uric acid can be analysed by energy dispersive x-ray microanalysis.

Calcium↗

Transitional cell papilloma of the bladder.

Bladder tumors of epithelial origin are rare in children. A 7-year-old male presented with intermittent painless hematuria. An ultrasound examination of the bladder revealed a single polypoid mass which proved to be a transitional cell papilloma.

Adolescent↗