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Biomedical subjects

L H Smith

Publications and source records attributed to L H Smith.

At least 55 records · Page 3Linked to original sources

Suture entrapment and secondary ureteral obstruction.

During the 6-year period ending in 1988, suture entrapment and secondary postoperative ureteral obstruction occurred in 18 (0.33%) of the 5379 patients who underwent major pelvic operations for benign conditions. Sixteen cases occurred after vaginal surgery and two after abdominal hysterectomy. Placement of the McCall suture or sutures for elevation of a bladder neck caused ureteral entrapment most frequently. Early diagnosis was facilitated by comparison of preoperative and postoperative serum creatinine levels. The mean change in serum creatinine level in patients with unilateral obstruction was an increase of 0.8 mg/dl. Treatment by either antegrade placement of ureteral stents or abdominal exploration with deligation or ureteroneocystotomy was successful in all cases. Retrograde placement of ureteral stents was unsuccessful.

Female↗

Diet and hyperoxaluria in the syndrome of idiopathic calcium oxalate urolithiasis.

Hyperoxaluria is an important risk factor in patients who form calcium oxalate stones within the urinary tract. It occurs in patients with primary hyperoxaluria, enteric hyperoxaluria, and the syndrome of idiopathic calcium oxalate urolithiasis. In the latter condition, the specific causes of the hyperoxaluria are not well defined. Diet and the availability of calcium and oxalate from the diet within the intestine are important factors in the hyperoxaluria that is present in some of these patients with idiopathic calcium oxalate urolithiasis. Other abnormalities in endogenous metabolism or transport of oxalate may play a role in the hyperoxaluria in some of these patients.

Calcium↗

Combined hepatic and renal transplantation in primary hyperoxaluria type I: clinical report of nine cases.

PURPOSE AND PATIENTS AND METHODS: The purpose of this article is to report the experience of three centers with combined hepatic and renal transplantation for pyridoxine-resistant primary hyperoxaluria type I (alanine:glyoxylate aminotransferase [EC 2.6.1.44] deficiency), with particular emphasis on the selection criteria and timing of the operation. Nine patients with this inherited disease were treated by combined hepatic and renal transplantation. The former replaces the enzyme-deficient organ while the latter replaces the functionally affected organ. RESULTS: One patient with gross systemic oxalosis died in the immediate postoperative period and another died 8 weeks postoperatively of a generalized cytomegalovirus infection, having shown evidence of biochemical correction. One patient with particularly severe osteodystrophy at the time of the operation died 14 months postoperatively from renal failure due to progressive calcium oxalate nephrocalcinosis involving the transplanted kidney, plus thromboembolic disease. He also had very extensive systemic oxalosis. An additional patient with severe osteodystrophy died 9 months postoperatively. One patient developed hyper-rejection of the kidney and died later of gastrointestinal hemorrhage. The four long-term survivors (22 to 38 months) have remained asymptomatic from the standpoint of their renal disease, with resolution of any manifestations of systemic oxalosis that they may have had. They are either employed or continuing their education. CONCLUSIONS: A prolonged period of end-stage renal failure treated by dialysis regimens that are suitable for non-hyperoxaluric renal failure and extensive systemic oxalosis, particularly oxalotic osteodystrophy, are poor prognostic features. We propose that hepatic transplantation should be considered as definitive treatment before end-stage renal failure develops. This should be supplemented by renal transplantation with vigorous pre- and perioperative hemodialysis to deplete the body stores of oxalate. Although some authorities would reserve hepatic transplantation for patients in whom renal transplantation has failed, we suggest that combined liver and kidney transplantation is appropriate in patients who have never had a renal graft. Furthermore, the time has come to consider hepatic transplantation before any irreversible renal damage has occurred in these patients.

Adolescent↗

Estrogen regulation of Xenopus laevis gamma-fibrinogen gene expression.

Albumin gene expression in Xenopus is regulated by estrogen through changes in the stability of its mRNA. The goal of the present study was to determine whether a similar pathway regulates gamma-fibrinogen. Degenerate oligonucleotides directed to conserved regions of the carboxyl-terminal half (domain D) of human and lamprey gamma-fibrinogen were used to isolate a full-length cDNA clone for Xenopus gamma-fibrinogen. Analysis of codon utilization from the DNA sequence of this clone revealed that Xenopus gamma-fibrinogen mRNA shows the same bias against CG dinucleotides as present in human, but not lamprey, fibrinogen mRNA. Features of the protein shared with the human homologue include all of the cysteine residues, an N-linked glycosylation site at amino acid 50, and 75% sequence identity in domain D. Much of the same region is conserved in lamprey gamma-fibrinogen. There is only a single size mRNA encoding gamma-fibrinogen in Xenopus, unlike rats where two mRNAs of different length are generated by alternate splicing. Administration of estrogen to male Xenopus results in the disappearance of gamma-fibrinogen mRNA from the cytoplasm, with no effect on steady-state levels in the nucleus. This process can be blocked by prior treatment with anti-estrogen, indicating that, like the regulation of serum albumin mRNA, gamma-fibrinogen is regulated posttranscriptionally through an estrogen receptor dependent mechanism. It is postulated that a consensus sequence flanking the AAUAAA polyadenylation signal in gamma-fibrinogen and the 68- and 74-kDa albumin mRNAs, but not vitellogenin or beta-globin mRNA, may play a role in the hormonal regulation of mRNA stability.

Amino Acid Sequence↗

Prospective randomized trial of topical alpha-interferon (alpha-interferon gels) for the treatment of vulvar intraepithelial neoplasia III.

Twenty-one patients were prospectively randomized into a blinded double-armed crossover study comparing alpha-interferon (alpha-IFN, 10(6) IU in a 3.5% aqueous methylcellulose base) with and without 1% nonoxynol-9. Nine and twelve patients were randomized to arms with (+N) and without (-N) 1% nonoxynol-9, respectively. Patients applied the gel to affected areas every 8 hr and were evaluated biweekly. Including those crossed over, 14 patients were treated with -N. Six of fourteen (43%) achieved complete responses: biopsy proven with at least 1 year follow-up (CR). One patient achieved a partial response with at least a 50% reduction in the total surface area of all lesions present (PR). Similarly, 13 patients were treated with +N. Two patients in this group were found to have invasive cancer and one to have HIV and thus were eliminated from statistical analysis. Of the remaining 10 patients, 3 had CRs (30%), 5 had PRs (50%), and 2 failed to respond. There was no significant difference in responses between the two groups. Overall, 14 of 18 (67%) patients demonstrated some response to alpha-IFN applied topically. These data support the conclusion that alpha-IFN is an active agent in the treatment of vulvar intraepithelial neoplasia III.

Administration, Topical↗

Study of the selective cytotoxic properties of cationic, lipophilic mitochondrial-specific compounds in gynecologic malignancies.

Cationic lipophilic compounds have a unique cytotoxic mechanism of action which is dependent on mitochondrial-specific localization of these fluorescent dyes. We have demonstrated in vitro that carcinoma cells, which have a higher negative mitochondrial membrane potential than normal cells, have an increased accumulation and retention of two of these compounds. The compounds tested were rhodamine 123 and dequalinium (DECA). After the development of a reproducible murine intraperitoneal (ip) human ovarian cancer model, which maintained the biologic characteristics of the parent cell line, we undertook in vivo evaluation of DECA. Mice with intraperitoneal tumor inoculations were treated with cisplatin, and/or DECA. When compared to cisplatin, a chemotherapeutic agent known to be effective in the treatment of clinical ovarian cancer, DECA was significantly more efficacious and seemed less toxic in the murine model. Cisplatin and DECA used together were possibly synergistic. Cationic lipophilic compounds may prove to be an exciting new class of antineoplastic agents which exploit intracellular, mitochondrial differences between normal cells and cancer cells.

Animals↗

Laxative abuse as a cause for ammonium urate renal calculi.

Nine women with laxative abuse and predominantly ammonium urate renal calculi underwent metabolic studies to identify common chemical abnormalities and determine pathophysiology. The 24-hour urine studies demonstrated marked decreases in volume (902 cm.3), sodium (28 mEq.), citrate (116 mg.) and potassium (21 mEq.). A significant elevation in ammonium urate supersaturation was found compared to control subjects when studied by the computer model EQUIL 2. Of the patients 7 had 1 or more urine specimens positive for phenolphthalein. Gastrointestinal loss of fluid and electrolytes allowed for chronic extracellular volume depletion. Intracellular acidosis was present as judged by low urinary citrate and potassium. The fact that the ion product for ammonium urate is increased significantly compared to controls reflects the stated pathophysiological changes. Laxative abuse should be suspected whenever a woman has an ammonium urate renal calculus in sterile urine.

Adult↗

Renal stones. Solutions and solute.

In the formation of calculi within the urinary tract, two fundamental factors are critical when crystals precipitate and stones form: They are solute and the solution itself, which must be oversaturated if crystals are to form and to grow. Several elements present in the urine influence solutions and solute and, thus, stone formation. Because all forms of medical therapy influence these elements favorably to prevent stone formation, this update reviews why stones form and how specific medical therapy works to prevent their formation.

Calcium Oxalate↗

Idiopathic calcium oxalate urolithiasis.

Approximately 70% of patients who form metabolic stones have the idiopathic calcium oxalate urolithiasis syndrome, which is diagnosed by exclusion of other identifiable metabolic abnormalities. This article reviews the classification, risk factors, and treatment options for those patients with this syndrome.

Calcium↗

Overview of hemochromatosis.

Hemochromatosis is an autosomal recessive genetic disorder that occurs with high prevalence in populations of European origin. The gene that is abnormal in hemochromatosis is found on the short arm of chromosome 6 in close proximity (approximately 1 centimorgan) to HLA-A, but the product coded for by that gene is unknown. The pathogenetic mechanism in hemochromatosis is that of continued, excessive absorption of dietary iron with loss of normal control mechanisms, leading to a gradual but vast expansion of storage iron as ferritin and especially as hemosiderin. Through mechanisms that probably include peroxidation of lipid membranes, the excess iron injures hepatocytes, islet B cells, gonadotropes in the anterior pituitary, myocardium, synovial cells, and chondrocytes, and probably other cells and tissues as well. Most patients with hemochromatosis remain undiagnosed throughout life. Removal of the excess iron by phlebotomy will prevent all of the complications of hemochromatosis when begun early and will significantly improve survival in virtually all patients. It is important, therefore, that the diagnosis of hemochromatosis be considered much more frequently in clinical medicine in order that this effective therapy be utilized.

Female↗

Evidence of calmodulin involvement in cell volume recovery following hypo-osmotic stress.

An influx of Ca2+ into red blood cells of the bivalve mollusc Noetia ponderosa occurs immediately following a hypo-osmotic stress. The volume recovery response to the stress is dependent upon [Ca2+]o and is inhibited by phenothiazines. The action of these drugs is on the amino acid regulation portion of the recovery rather than on the ionic portion. Since the phenothiazines are non-specific in action, we have conducted several experiments to decide the site of phenothiazine action on the volume recovery response. The sulfoxide derivatives of both chlorpromazine and trifluoperazine have no effect on volume regulation at the same dose where the parent compound inhibits. At 50-100 times the concentration of the parent compound, the derivatives block both volume regulation and taurine efflux. The phorbol ester, TPA, an activator of protein kinase C, alters the volume recovery, but does so by affecting K+ rather than amino acid regulation. The only phenothiazine target that we can not rule out is calmodulin, which we also demonstrate to be present in the clam red cells. Thus, the data presented suggest that calmodulin is involved in the amino acid regulatory portions of the volume recovery in response to hypo-osmotic swelling.

Animals↗

The medical aspects of urolithiasis: an overview.

An overview of the medical aspects of urolithiasis is presented. The physicochemical factors in the formation of a stone within the urinary tract are reviewed, including supersaturation, nucleation sites and mechanisms of crystal formation and retention, and modifiers of crystal formation, including promoters and inhibitors. Finally, some directions for future research in urolithiasis are identified.

Humans↗