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R P Walker

Publications and source records attributed to R P Walker.

35 records · Page 2Linked to original sources
PubMed1996

Laser-assisted uvulopalatoplasty: postoperative complications.

Laser-assisted uvulopalatoplasty (LAUP) has become a widely used procedure for the treatment of snoring and mild sleep apnea in the United States. Between July 1993 and December 1994, the authors of this study prospectively evaluated 541 consecutive patients referred to their hospital for possible LAUP to treat loud disruptive snoring. Of the 541 patients, 275 patients had a total of 754 LAUP procedures. There were 26 complications (3.45%). These complications included postoperative hemorrhage in 16 patients (2.12%), local infection in 4 patients (0.53%), temporary palatal incompetence in 4 patients (0.53% , and temporary loss of taste in 2 patients (0.27%). None of the 16 patients with postoperative hemorrhage required a blood transfusion. Only 10 patients (1.3%) had hemorrhage that required medical attention; in the other patients, the bleeding stopped spontaneously. There were no cases of hypernasal speech, permanent palatal incompetence, nasopharyngeal stenosis, airway compromise, or death.

Adult↗
PubMed1996

Objective assessment of snoring before and after laser-assisted uvulopalatoplasty.

Laser-assisted uvulopalatoplasty (LAUP) is an outpatient staged surgical procedure for the treatment of snoring. Each patient undergoes a series of procedures with the end point being patient and bed partner satisfaction in most cases. The purpose of this study was to objectively evaluate the frequency, pattern, and volume of snoring in patients prior to and following each LAUP procedure. A sonographic device, SNAP, which records oronasal respiration, was used to assess patients at home. A digital analysis of the frequency, pattern, and volume was then performed. Twenty-seven patients have been completely evaluated with this recording device. The findings demonstrate that the LAUP procedure alters the snoring sound. The maximum, average, and velum-like respiratory noise loudness all showed a statistically significant decrease when comparing the preoperative snoring to the final recording after treatment was completed. In addition, the fundamental frequency of the snoring increased significantly after each LAUP procedure. No change was seen in the snoring index following treatment. These objective results correlated well with the subjective responses of the patients and their bed partners. These findings are consistent with the hypothesis that the LAUP procedure alters snoring in a favorable manner by both objective data and subjective accounts.

Female↗
PubMed1995

Purification, and phosphorylation in vivo and in vitro, of phosphoenolpyruvate carboxykinase from cucumber cotyledons.

Phosphoenolpyruvate carboxykinase (PEPCK) with a subunit molecular mass of 74 kDa has been purified 450-fold to homogeneity from the cotyledons of cucumber (Cucumis sativus L.). This is the first purification of the native form of the enzyme from any plant tissue. Incubation of the purified enzyme with [gamma-32P]ATP and either phosphoenolpyruvate-carboxylase kinase or mammalian cAMP-dependent protein kinase led to labelling of the enzyme in a part of the molecule separate from the active site. This was reversed by incubation with protein phosphatase 2A. Cotyledons of cucumber seedlings were also supplied with 32Pi. Homogenates of such cotyledons contained a heavily labelled polypeptide which was confirmed as PEPCK by immunoprecipitation. Labelling of PEPCK by 32Pi in darkened cotyledons was reversed by illumination.

Amino Acid Sequence↗
PubMed1995

Second-trimester levels of maternal urinary gonadotropin peptide in Down syndrome pregnancy.

Urinary gonadotropin peptide (UGP; beta-core fragment), a major metabolite of human chorionic gonadotropin (hCG), was shown recently to be markedly elevated in Down syndrome pregnancy between 19 and 22 weeks of gestation. To confirm and extend this finding, we obtained maternal urine and matching maternal serum samples from 14 cases of Down syndrome and six other aneuploidies between 17 and 21 weeks of gestation. UGP was measured in all these samples and in 91 singleton control urines. Results were corrected for urinary creatinine level and expressed as multiples of the control median (MOM). hCG levels were assayed in all serum samples from the cases and compared with previously established reference values. The median UGP level in Down syndrome cases was 5.34 MOM (range 2.71-12.57); 88 per cent of the values were above the 95th centile of control levels after modelling. The median maternal serum hCG level for the same cases was 2.20 MOM (range 0.84-3.40); 36 per cent of the values were above the 95th centile. The level of UGP in every case including all other aneuploidies was higher than the comparable maternal serum hCG level. Elevated UGP measurements are strongly associated with fetal Down syndrome during the second trimester and could contribute to improved Down syndrome screening protocols that are more accessible and less expensive than are currently available.

Adult↗
PubMed1995

Nodular disease during pregnancy.

The incidence of autoimmune disease of the thyroid approaches 10% in women. This autoimmune state, which predisposes to the development of thyroid neoplasia, especially in patients with subclinical hypothyroidism, combined with tumor growth and immunologic factors that occur in the pregnant state, account for the significant incidence of nodular thyroid disease in pregnancy. Thyroid carcinoma of follicular cell origin in a young woman can generally be expected to pursue a slow course with ample time for preoperative preparation and operative treatment. However, the pregnant state should be considered an exception and thyroid nodular disease with suspicious aspiration cytologic features should be managed with a certain degree of urgency. In an excellent article on the subject of pregnancy as a predisposing factor in thyroid neoplasia, Rosen and Walfish present a series of 30 patients with thyroid neoplasia arising during pregnancy. The incidence of thyroid carcinoma was 43% and the incidence of adenoma 37%, for an 80% overall incidence of neoplasia. Furthermore, during the course of the pregnancy, 20% of the patients showed marked increase in nodular growth, including a 26-year-old primiparous woman who developed a small nodule in the first trimester which proved to be cellular on needle aspiration biopsy. In spite of thyroid hormone treatment, the nodule grew markedly in the last trimester. At postpartum operation, the patient was found to have a papillary carcinoma with extensive unilateral neck and mediastinal node disease, which was clinically occult. These authors stress the importance of the operative treatment of thyroid neoplasia of pregnancy, either in the second trimester or immediately after delivery. We agree.

Adult↗
PubMed1995

Laser-assisted uvulopalatoplasty for snoring and obstructive sleep apnea: results in 170 patients.

Laser-assisted uvulopalatoplasty (LAUP) is a procedure for the treatment of snoring and, possibly, sleep apnea. Between July 1993 and December 1994, the authors prospectively evaluated 541 consecutive patients referred to their teaching hospital for possible LAUP to treat loud, disruptive snoring. Of these patients, 274 (51%) had one or more LAUP treatments. As of January 1995, LAUP treatment courses were completed in 170 patients. In this paper, the authors report preliminary results on the use of LAUP in these patients. Among the 170 patients, 105 (62%) had a diagnosis of snoring and 65 (38%) obstructive sleep apnea syndrome (OSAS) based on preoperative polysomnography. LAUP treatment in the snoring only patients resulted in complete or nearly complete elimination of snoring in 63 patients (60%), partial improvement of snoring in 30 patients (29%), and no improvement in 11 patients (10%). Of the 65 OSAS patients treated with LAUP, postoperative polysomnograms were obtained in 33 patients (51%). Surgical success was achieved in 16 (48%) of the 33 patients. However, 7 patients (21%) had repeat polysomnograms that were worse than their preoperative polysomnograms, and 5 patients (15%) had no significant change. The results of this study suggest that LAUP may be a viable surgical option for patients with snoring and mild sleep apnea.

Adult↗
PubMed1994

Parathyroid autotransplantation in patients undergoing a total thyroidectomy: a review of 261 patients.

Parathyroid autotransplantation was first described in 1907 by Halsted. However, this simple and effective method of preserving parathyroid function has been used with increasing frequency only during the past 25 years. Beginning in the late 1960s, our group has transplanted normal parathyroid tissue into the ipsilateral sternocleidomastoid muscle whenever these glands could not be preserved in situ with adequate blood supply. In addition, if the blood supply of all four parathyroid glands appeared compromised, cryopreservation of parathyroid tissue was performed in case the autotransplanted tissue did not function after surgery. Since 1970, 393 patients underwent a total thyroidectomy. Parathyroid glands that could not be saved in situ were biopsied to confirm their identity by frozen section and then autotransplanted. Of the 393 patients who underwent a total thyroidectomy, 261 patients required transplantation of one or more glands. Among those 261 patients who underwent selective parathyroid autotransplantation, 33 (13%) required temporary calcium and vitamin D supplementation. Of these 33 patients, 2 (less than 1%) had permanent hypoparathyroidism and are receiving long-term vitamin D therapy.

Adolescent↗
PubMed1993

Hyperparathyroidism induced by hypothyroidism.

The coexistence of hyperparathyroidism and thyroid tumors and/or chronic thyroiditis has raised the possibility of an etiologic relationship. The present study was designed to test the hypothesis that the chronic elevation of thyroid-stimulating hormone (TSH) is related to the development of hyperparathyroidism. Three groups of 24 rats each were treated for 12 weeks as follows: group 1 received propylthiouracil (PTU) in their deionized water; group 2 received PTU and thyroid hormone to suppress TSH and to serve as a control group for possible direct effects of PTU; and group 3 was not treated at all and served as another control group. At 12 weeks, 95% of group 1 rats (PTU only) showed hyperplasia of the parathyroids with a 30% mean increase in circulating parathormone.

Administration, Oral↗
PubMed1992

Gibberellin perception and the Avena fatua aleurone: do our molecular keys fit the correct locks?

The plant hormones GA, ABA, and auxin differ from the majority of animal hormones in that they are hydrophobic weak acids. They are soluble in the inter- and intra-cellular environments of plant tissues and their neutral species can cross the plasma membrane by passive diffusion. Auxin transport is mediated by specific uptake and efflux carriers in plasma membranes, and there is some evidence for carrier-mediated uptake of GA and ABA. Because these plant hormones can cross the plasma membrane it is not a prerequisite that receptors for them should be at the protoplast surface. Nevertheless, there is substantial evidence that auxin acts at the plasma membrane, and evidence suggesting that GA may be perceived at the plasma membrane of A. fatua aleurone protoplasts has been reviewed here. It is conceivable that the plant plasma membrane might provide the means to integrate, transduce, and amplify these signals, and that such properties of the plasma membrane, rather than the permeability characteristics of these ligands, may determine the site of perception. Further progress in our understanding of signal transduction pathways that may be involved in the actions of plant hormones is likely to shed light on these questions. It has been proposed that GA receptors involved in cell elongation may be soluble rather than membrane bound. The soluble 50 kDa GA-binding protein observed in aleurone by GA4 photoaffinity labelling may be a good candidate for a soluble GA receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Anti-Idiotypic↗
PubMed1990

The relationship between Hashimoto's thyroiditis, thyroid neoplasia, and primary hyperparathyroidism.

The relationship between Hashimoto's thyroiditis and follicular cell carcinoma of the thyroid remains controversial. Hashimoto's thyroiditis is regarded by some as a premalignant lesion for which thyroidectomy is definitely indicated. In contrast, other investigators have found no increased evidence of thyroid carcinoma in patients with this disease. As a result, the management of thyroid nodules in patients with Hashimoto's thyroiditis remains highly individualized. A program for the management of patients with chronic Hashimoto's thyroiditis with co-existing neoplasia or primary hyperparathyroidism is outlined.

Adenocarcinoma↗
PubMed1989

Metabolic activation of 6-nitrochrysene in explants of human bronchus and in isolated rat hepatocytes.

It has previously been shown that 6-nitrochrysene can be activated to electrophilic species capable of reacting with DNA through metabolic pathways that form N-hydroxy-6-aminochrysene or trans-1,2-dihydroxy-1,2-dihydro-6-aminochrysene as critical intermediates. Since the lung is a known target tissue for the carcinogenic action of polycyclic nitroaromatic hydrocarbons, we investigated the metabolism and DNA binding of [3H]6-nitrochrysene in 11 specimens of human bronchus. Analysis of medium from [3H]6-nitrochrysene-treated explants indicated the presence of trans-9,10-dihydroxy-9,10-dihydro-6-nitrochrysene (0.04-330 pmol/mg epithelial DNA), trans-1,2-dihydroxy-1,2-dihydro-6-nitrochrysene (12-1700 pmol/mg epithelial DNA), 6-aminochrysene (1.6-2200 pmol/mg epithelial DNA), and trans-1,2-dihydroxy-1,2-dihydro-6-aminochyrsene (3.6-610 pmol/mg epithelial DNA). Both the levels and the relative proportions of these metabolites varied widely in explants from different individuals. The amount of DNA recovered and the level of DNA modification were sufficient for adduct analysis in eight of the 11 cases for which metabolite data were obtained. Five additional bronchial specimens for which metabolite data were not obtained were also analyzed for carcinogen-DNA adducts. The levels of binding varied from 0.06 to 30.5 pmol [3H]6-nitrochrysene bound/mg DNA (two adducts per 10(8) nucleotides-10 adducts per 10(6) nucleotides). HPLC analyses of enzymatic hydrolysates of the explant DNA indicated that 11 of 13 cases contained adducts with retention times identical to those of adducts derived from trans-1,2-dihydroxy-1,2-dihydro-6-aminochrysene or N-hydroxy-6-aminochrysene. The adduct derived from trans-1,2-dihydroxy-1,2-dihydro-6-aminochrysene was the major adduct detected in eight of 13 cases. The reasons for the variation in metabolism and adduct formation observed in [3H]6-nitrochrysene-treated explants of bronchus from different donors are not known but may reflect differences in the activities of enzymes responsible for the metabolism of this compound. The influence of induction of drug metabolizing enzymes on the activation pathway of 6-nitrochrysene in an intact cell system was tested using rat hepatocytes. 6-Nitrochrysene was incubated with freshly isolated hepatocytes from rats that were either untreated or pretreated with phenobarbital, 3-methylcholanthrene or Aroclor 1254. Although the levels of adducts were similar in all cases, the pattern of DNA adducts formed in these hepatocytes was dependent on the nature of the pretreatment of the rats. As previously reported, hepatocytes from untreated rats contained adducts derived from N-hydroxy-6-aminochrysene.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Metabolism of the carcinogen [3H]6-nitrochrysene in the preweanling mouse: identification of 6-aminochrysene-1,2-dihydrodiol as the probable proximate carcinogenic metabolite.

6-Nitrochrysene (NC) is a potent lung and liver carcinogen when administered in multiple doses to preweanling mice. We have investigated both the in vitro metabolism of [3H]NC by 9000 g supernatants (S9) prepared from the livers of preweanling mice and the in vivo metabolism of [3H]NC in these animals. The in vitro covalent binding of primary metabolites of NC to DNA after further reductive and/or oxidative metabolism was then examined in an attempt to define the metabolic activation pathway responsible for the formation of carcinogen--DNA adducts in NC-treated preweanling mice. NC-1,2-dihydrodiol, NC-9,10-dihydrodiol, 6-aminochrysene (AC), and several unidentified compounds were found in ethyl acetate extracts of incubations containing [3H]NC and liver S9 from 1- or 8-day-old BLU:Ha mice. Comparison of the in vivo metabolism of NC in 1-day-old animals and 8-day-old animals which had been treated with NC on day 1 indicated that the formation of AC and the two NC dihydrodiols was greater in the younger animals. Further metabolism of NC-1,2-dihydrodiol by S9 from 8-day-old mice yielded AC-1,2-dihydrodiol as a major product. Incubation of AC-1,2-dihydrodiol, calf thymus DNA and liver microsomes from 3-methylcholanthrene-induced rats yielded a single major adduct that was chromatographically and chemically identical to the major adduct formed in [3H]NC- and [3H]-AC-treated preweanling mice. The results indicated that the major DNA adduct found in vivo is derived from the further metabolism of the proximate carcinogen AC-1,2-dihydrodiol.

Animals↗
PubMed1987

Carcinogen-DNA adduct formation in the lungs and livers of preweanling CD-1 male mice following administration of [3H]-6-nitrochrysene, [3H]-6-aminochrysene, and [3H]-1,6-dinitropyrene.

6-Nitrochrysene (NC) and 6-aminochrysene (AC) have been shown to be potent lung and liver carcinogens when administered in multiple i.p. doses to preweanling mice. 1,6-Dinitropyrene has been shown to be a strong hepatocarcinogen but a weak lung carcinogen in this same bioassay. We have examined carcinogen-DNA adduct profiles in the target tissues of preweanling male CD-1 mice following administration of single or multiple doses of these compounds. Depending on the tissue and the dosing schedule, the total level of DNA modification in animals dosed with [3H]NC was 2- to 9-fold higher than in animals dosed with [3H]AC. Regardless of the dosing schedule, DNA isolated from the lungs and livers of both [3H]NC- and [3H]AC-treated preweanling male mice contained a single major and chromatographically identical adduct. This major adduct, which accounted for as much as 90% of the total carcinogen-DNA adducts in enzymatic hydrolysates from treated animals, was chromatographically distinct from the major C8-purine-substituted adducts formed from the reaction of N-hydroxy-AC with calf thymus DNA. In contrast to the results obtained with NC and AC, the major carcinogen-DNA adduct formed in the livers of mice treated with [3H]-1,6-dinitropyrene was found to cochromatograph with 1-N-(deoxyguanosin-8-yl)amino-6-nitropyrene, a product derived from N-hydroxy-1-amino-6-nitropyrene. Since NC and its nitro-reduced derivative, AC, yielded an identical carcinogen-DNA adduct in vivo and this adduct was not derived from N-hydroxy-AC, we conclude that the metabolic activation of NC in the neonatal mouse must involve some previously undescribed combination of ring-oxidation and nitro-reduction pathways. This activation pathway could be an important factor in determining the potency of NC and AC as carcinogens in this bioassay system.

Animals↗
PubMed1987

Identification of C8-modified deoxyinosine and N2- and C8-modified deoxyguanosine as major products of the in vitro reaction of N-hydroxy-6-aminochrysene with DNA and the formation of these adducts in isolated rat hepatocytes treated with 6-nitrochrysene and 6-aminochrysene.

Since 6-nitrochrysene and 6-aminochrysene have shown activity in carcinogenicity bioassays, we have begun an investigation of their metabolic activation pathways and the nature of the carcinogen-DNA adducts that may be formed. N-Hydroxy-6-aminochrysene (N-hydroxy-AC), a candidate proximate or ultimate carcinogen and the highest polycyclic N-hydroxy arylamine homolog studied thus far, was prepared by direct chemical synthesis and characterized by 1H-n.m.r. spectroscopy. Its rate and extent of reaction with DNA in vitro was 20-30 nmol bound/mg DNA/30 min, which is 2-10 times greater than has been reported for several other carcinogenic N-hydroxy arylamines. Three major aminochrysene-nucleoside adducts were detected in enzymatic hydrolysates of this N-hydroxy-AC-modified DNA, and these were isolated and identified by mass and 1H-n.m.r. spectroscopy as N-(deoxyinosin-8-yl)-6-aminochrysene, 5-(deoxyguanosin-N2-yl)-6-aminochrysene, and N-(deoxyguanosin-8-yl)-6-aminochrysene. These adducts accounted for 32%, 28%, and 22% respectively, of the total DNA adducts formed. We hypothesize that the deoxyinosine adduct is derived from spontaneous oxidation of the corresponding deoxyadenosine adduct prior to or during DNA isolation and adduct preparation. DNA isolated from Sprague-Dawley rat hepatocytes which had been treated with [3H]6-aminochrysene or [3H]6-nitrochrysene contained up to 12 pmol adducts/mg DNA (4 adducts per 10(6) nucleotides). High performance liquid chromatography (h.p.l.c.) analyses of enzymatic hydrolysates of this DNA indicated that the major products formed cochromatographed with the C8-deoxyinosine and C8-deoxyguanosine adducts. N-(Deoxyinosin-8-yl)-6-aminochrysene and N-(deoxyguanosin-8-yl)-6-aminochrysene accounted for 45% and 30% respectively, of the total DNA adducts formed in these cells. The preferential modification of deoxyadenosine by N-hydroxy-6-aminochrysene and the apparent facile oxidation of this adduct to a deoxyinosine derivative is thus far unique among the reactions of N-hydroxyarylamines with DNA and would not be predicted on the basis of reactivity alone.

Animals↗
PubMedDate not supplied

The role of intestinal microflora in the metabolic activation of 6-nitrochrysene to DNA-binding derivatives in mice.

6-Nitrochrysene has previously been shown to be a potent lung and liver carcinogen following i.p. administration to newborn mice and to be metabolically activated to DNA-binding derivatives by nitro-reduction or a combination of nitro-reduction and ring oxidation. In this study, we have examined fecal metabolites and DNA-carcinogen adducts in 5-week-old conventional and germfree Balb/c mice treated with [3H]6-nitrochrysene in order to determine if the metabolic activation pathway(s) for this compound in these mice differs from that observed in preweanling mice. We further evaluated the role of the intestinal microflora on the metabolism and generation of DNA-reactive metabolites in this system. The amount of 6-aminochrysene excreted in the feces of germfree mice within 48 h after treatment with a single i.p. dose of [3H]6-nitrochrysene (0.03 mumol/5 microliters/g body wt) was approximately 25% of that excreted in identically treated conventional mice. However, the levels of carcinogen-DNA adducts in the lungs and livers of conventional and germfree Balb/c mice were similar at the 24 and 48 h time points examined. HPLC analysis of hydrolysates of liver and lung DNA indicated that adducts derived from both N-hydroxy-6-aminochrysene and trans-1,2-dihydroxy-1,2-dihydro-6-aminochrysene metabolites were formed in the liver whereas only the latter adduct was detected in the lung. This contrasts with previous findings in preweanling mice where the adduct derived from the trans-1,2-dihydroxy-1,2-dihydro-6-aminochrysene metabolite was the single major adduct detected in both liver and lung DNA. The proportion of adducts derived from N-hydroxy-6-aminochrysene was significantly greater in the liver DNA of germfree mice than in the liver DNA of conventional mice.

Animals↗
PubMedDate not supplied

UGP--a tumor marker of gynecologic and breast malignancies? Specificity and sensitivity in pretherapeutic patients and the influence of hormonal substitution on the expression of UGP.

Urinary gonadotropin peptide (UGP) is a 10,300 Dalton peptide which is present in the urine of pregnant women, those with trophoblast disease and those with, certain nontrophoblastic malignancies. We examined the efficiency of UGP measurement at differentiating benign from malignant gynecologic and breast diseases. UGP was measured in 1355 spot urine samples from 841 patients (343 samples from 323 healthy women and women with benign gynecologic and breast diseases, 1012 samples from 518 women with gynecologic malignant diseases or breast cancer). Using a cutoff of > 3 fmol UGP/mg urinary creatinine the specificity was 97%. The sensitivity of UGP was calculated from pretherapeutically collected samples (n = 210). The sensitivity of the test for all malignancies was 26% (ovarian malignancy (n = 27) 52%, endometrial cancer (n = 25) 32%, cervical cancer (n = 49) 29%, breast cancer (n = 72) 19%, vulvar cancer and vaginal cancer (n = 12) 17% and for carcinoma in situ of the breast or the cervix (n = 20) 0%). We also found significantly higher UGP values in postmenopausal women than in premenopausal women. Hormonal substitution significantly lowered the UGP values.

Biomarkers, Tumor↗