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Biomedical subjects

L H Smith

Publications and source records attributed to L H Smith.

At least 19 recordsLinked to original sources

Role of ultrasound in medical management of patients with renal stone disease.

Eighty-three patients with radiographically opaque renal stones were evaluated prospectively with ultrasound and compared to KUB (kidneys, ureters, bladder) with tomograms (KUB/T) to further define the use of ultrasound in the evaluation of renal calculi. The presence or absence and the size, number, and location of stones were analyzed and correlated for each modality. Ultrasound detected the presence of renal stones in 77 of 83 (93%) patients. However, all of the stones were detected on ultrasound in only 60% of these patients. Thirty percent (80 of 269) of the papillary-calyceal stones seen on KUB/T were missed on US; 66% of the stones missed measured 2 mm or less. Although ultrasound can be used for detection of intrarenal stones, KUB/T is a more accurate imaging examination for determination of size and number of small stones.

Adolescent

Human monoclonal antibody recognizing an antigen associated with ovarian and other adenocarcinomas.

MS2B6, a human monoclonal antibody derived from a patient with advanced ovarian cancer, has been used to study the distribution and characteristics of its target antigen. The MS2B6 antigen was detected by immunoperoxidase studies in 41 of 41 epithelial ovarian cancers and in the majority of nonovarian adenocarcinomas. Among normal tissues the MS2B6 antigen was found in the adult epithelia of the fallopian tube, endometrium, endocervix, colon, bronchus, breast, sweat duct, and large renal ducts. No detectable antigen was found in peritoneal epithelia, tissue stromal cells, spleen, thymus, or blood-borne cells. Immunoblotting analysis showed that the MS2B6 epitope resides on polypeptides of 38, 44, and 60 kd. The cellular location of the MS2B6 antigen was studied with immunoperoxidase and immunofluorescent staining and immunoelectronmicroscopy of ovarian cancer ascites tumor cells. The results suggest that in ascites tumor cells the MS2B6 antigen is located in a layer of the peripheral cytoplasm beginning just below the cell membrane. MS2B6 may be useful as an imaging or therapeutic agent.

Adenocarcinoma

Synchronous radiation and cytotoxic chemotherapy for locally advanced or recurrent squamous cancer of the vulva.

Between July 1987 and September 1991 a program of external beam radiation and synchronous, radiopotentiating chemotherapy was employed to treat 25 women with locoregionally advanced or locoregionally recurrent squamous cancer of the vulva. Of 18 previously untreated patients, 1 was Stage II, 10 were Stage III, 6 were Stage IVA, and 1 was Stage IVB. Reasons for patient referral for nonsurgical management included the presence of initially unresectable disease (5 patients), disease extent which would have necessitated partial or total exenteration if treated surgically (9 patients), disease extent predictive of inadequate surgical margins (less than 1 cm gross margin) if treated by less than exenterative surgery (8 patients), and severe comorbid illness precluding surgical management (3 patients). Complete clinical response was obtained in 16 of 18 previously untreated patients (89%) and in 4 of 7 patients with recurrent disease following vulvar surgery (57%). Of 20 patients achieving a complete clinical response, 3 patients have relapsed within the irradiated volume at 11, 38, and 48 months following completion of treatment. Fourteen patients remain alive and continuously cancer free from 2-52 months after completion of treatment (median follow-up 24 months). This experience suggests that initial management with radiation and chemotherapy may offer some patients with locally advanced squamous cancer of the vulva an alternative to exenterative surgery and may hold curative potential for some patients with surgically unresectable or medically inoperable disease.

Adolescent

Formation of a vagina at the time of exenteration.

The formation of an artificial vagina at the time of exenteration has been described. Femoral gluteal flaps forming a tube suspended to the iliopectineal ligament appeared to give the most satisfactory results.

Adult

Adenocarcinoma-reactive human monoclonal antibody MS2B6 defines an antigen in simple glandular epithelium.

A human monoclonal antibody (MAb), MS2B6, produced from splenocytes isolated from a patient with advanced papillary serous cystadenocarcinoma of the ovary, defines a unique human tumor-associated antigen. This antigen, EA2B6 (epithelial antigen 2B6), is expressed in a tissue-restricted manner on cultured and fresh human adenocarcinomas and some normal glandular epithelial tissues. EA2B6 is a 38-48 kD protein antigen that co-fractionates with the nuclear matrix-intermediate filament scaffold of simple glandular epithelial tissues. EA2B6 is a molecule with restricted solubility, and in vitro antigen-antibody binding is dependent on the antigen being presented on a solid support. To determine if EA2B6 is a cytokeratin, competition studies were undertaken with several cytokeratin-specific murine monoclonal antibodies. None of these antibodies inhibited the binding of human MAb MS2B6 to partially purified EA2B6. Less than 1% of HT29 colon adenocarcinoma cells and fresh ovarian adenocarcinoma ascites cells express EA2B6 on their surface. The majority of EA2B6 is intracellular. Because of the restricted tissue distribution of this antigen and stability of the antibody, we believe MS2B6 is a good candidate for MAb-mediated diagnosis and therapy of human adenocarcinomas.

Adenocarcinoma

Management of neutropenic enterocolitis in the patient with cancer.

Neutropenic enterocolitis is a life-threatening condition often seen in patients experiencing prolonged periods of neutropenia from conditions such as leukemia and lymphoma and from aggressive chemotherapy regimens. Its exact pathologic process remains unclear; however, it has been proposed that direct cytotoxic damage occurs to the bowel mucosa with subsequent microbial invasion complicated by the lack of adequate neutrophil response. The damage may progress to bowel perforation and septic shock. Early recognition and management by healthcare team members are crucial for the improved prognosis of these individuals. Controversy continues to exist concerning management options and the timing of these interventions. This article outlines nursing and medical management of the patient with neutropenic enterocolitis.

Enterocolitis

National High Blood Pressure Education Program (NHBPEP) review paper on complications of shock wave lithotripsy for urinary calculi.

This decade has witnessed dramatic advances in the surgical management of urinary calculi. Today, most stones can be removed by minimally invasive means. In fact, the treatment of choice in 60% to 90% of patients with renal and ureteral calculi that need to be surgically removed is extracorporeal shock wave lithotripsy (ESWL). This article reviews indications for ESWL and discusses deleterious effects of ESWL.

Animals

Passive membrane properties and inward calcium current of human uterine smooth muscle cells.

Human myometrium was obtained at the time of cesarean delivery by means of excisional biopsy from the upper margin of the uterine incision through the lower uterine segment. Isolated smooth muscle cells were obtained by collagenase treatment. With the whole-cell patch clamp technique, voltage-clamp and current-clamp experiments were performed. Regenerative action potentials were seen in 3 mmol/L calcium bathing solution. Voltage-clamp experiments demonstrated the presence of transient inward currents and large outward currents. Inward currents were isolated with the use of tetraethylammonium ion as a blocking agent of outward current. In 3 mmol/L calcium inward current began at -60 mV and maximum inward current occurred at -40 mV. Maximum inward current density during the rising phase of the action potential was 1.0 microA/cm2 in 3 mmol/L calcium and was unaffected by reduction of sodium concentration in the bathing solution.

Action Potentials

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