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Biomedical subjects

S Adams

Publications and source records attributed to S Adams.

At least 91 records · Page 5Linked to original sources

[Clinical value of somatostatin receptor scintigraphy. Studies of pre- and intraoperative localization of gastrointestinal and pancreatic tumors].

BACKGROUND: [111In-DTPA-D-Phe1]-pentetreotide scintigraphy is able to detect neuroendocrine tumors not shown by radiological methods. PATIENTS AND METHODS: In 270 patients with neuroendocrine gastroenteropancreatic tumors (GEP tumors) 400 somatostatin receptor scintigraphies were performed. 70 patients (38 female, 32 male, aged 28 to 74 [56 +/- 12.6] years) underwent surgery and follow-up over 2 years. The aim of the present study was the comparison of preoperative somatostatin receptor scintigraphy with radiological methods (sonography, CT) and intraoperative localization of GEP tumors with a hand-held gamma-probe. RESULTS: Somatostatin receptor scintigraphy was successful in localizing primary tumors in all patients. Liver- and lymph node metastases could be visualized with a sensitivity of 94 and 95 percent. In 7 patients 35 lesions could be identified by intraoperative tumor localization using a hand held gamma probe. Radiological methods identified only 11, surgical palpation 15 and preoperative somatostatin receptor scintigraphy 27 lesions. CONCLUSION: Somatostatin receptor scintigraphy improves detection of small and occult GEP tumors. Intraoperative probe counting with a hand-held gamma probe can identify tumors even when they are small and impalpable, but receptor positive.

Adult↗

Histology/cytology discrepancies in HIV-infected obstetric patients with normal pap smears.

OBJECTIVE: To estimate the frequency of cervical cytologic/histologic discrepancies in a group of obstetric patients diagnosed as HIV infected by routine prenatal screening. Also, to determine if serum CD4 levels or sexually transmitted diseases (STDs) are associated with the occurrence of preinvasive cervical disease in these women. METHOD: Thirty-two women who presented for routine prenatal care to Medical Center of Louisiana were diagnosed as HIV infected by ELISA and Western blot testing and had normal Pap smears. These patients then agreed to undergo the following: colposcopy with directed biopsies; chlamydia, gonorrhea, and syphilis screening; and serum CD4 level. RESULTS: No patients had AIDS-defining diagnoses other than CD4 < 200/mm3. Ten of 32 (31%) had cervical intraepithelial neoplasia (CIN) despite normal cytology. Six of 32 (19%) had STDs. One of 10 in the group with CIN had a STD. The mean CD4 level in those patients with CIN was 249/mm2 (range 1-524) vs 501/mm2 (range 210-979) in those without CIN. (P = 0.0118) CONCLUSIONS: Newly diagnosed HIV-infected pregnant women without clinical evidence of AIDS are noted to have CIN at a rate similar to nonpregnant HIV-infected women. The Pap smear appears to have a significant false-negative rate in this group. STDs, while common, were not directly associated with false-negative Pap smears. CIN is associated with immunosuppression, as measured by low CD4 counts.

Adolescent↗

The effect of omeprazole pretreatment on acetaminophen metabolism in rapid and slow metabolizers of S-mephenytoin.

Omeprazole, a widely used and potent gastric proton pump inhibitor, induces cytochrome P450 (CYP) 1A2 in humans. Induction is most pronounced in slow metabolizers of S-mephenytoin because CYP2C19 (S-mephenytoin hydroxylase) is responsible for the elimination of omeprazole. Acetaminophen (INN, paracetamol), a widely used and effective analgesic and antipyretic agent, causes serious hepatic and renal toxicity at high doses by conversion of acetaminophen to the toxic intermediate N-acetyl-p-benzoquinone imine (NAPQI) through CYP1A2, CYP2E1, and CYP3A4. This study evaluated whether omeprazole pretreatment in five rapid and five slow metabolizers of S-mephenytoin could increase thioether (an estimate of NAPQI production) metabolite formation from acetaminophen. The results of this study show that, despite induction of CYP1A2 activity in slow metabolizers (a 75% increase in plasma clearance of caffeine), the formation of NAPQI from acetaminophen was not increased after 7 days of omeprazole administration (40 mg/day). This suggests that induction of CYP1A2 activity by omeprazole is unlikely to increase the risk of acetaminophen hepatotoxicity.

Acetaminophen↗

Medication, chronic illness and identity: the perspective of people with asthma.

The issue of compliance with prescribed medication has traditionally been dominated by the perspective of the health professional although increasingly sociologists, using qualitative methods, have begun to present the patients' point of view. However, little has been published on asthma, despite the numbers of people suffering from this chronic condition and the amount of medication regularly prescribed. This paper focuses on the perspective of a sample of S. Wales (U.K.) asthma patients who have all been prescribed prophylactic medication in the last 12 months and explores their attitudes to medication in the context of their everyday lives, using inductive qualitative research methods. Two main groups were identified: the deniers and the accepters. They differed fundamentally in their readiness to accept the identity of asthma sufferer which, in turn, was associated with very different beliefs about the nature of their problem and the meaning of the medication prescribed for it. There was also marked differences in their strategies of self-presentation and disclosure and their pattern of medication use, particularly for prophylactic medication. A third group, the pragmatists, were also identified as a possible sub-group of the accepter category who are less open within self-presentation and less consistent in their beliefs about asthma but do not reject the label entirely. Identity work, i.e. the way the respondents interpreted the social identity of asthma sufferers and managed to reconcile it with other social identities, is proposed as the most useful way of understanding the observed variation in the way people diagnosed as asthmatic conceptualise and use their medication.

Adolescent↗

Gel microdrop technology for rapid isolation of rare and high producer cells.

Secreted proteins are a therapeutic cornerstone of the biotechnology industry, and numerous recombinant products, including human growth hormone, human erythropoietin and granulocyte-colony stimulating factor, are now widely prescribed. In addition to bioprocessing applications, GMD technology should benefit the emerging fields of cellular and gene therapy. The ability to assess rapidly and precisely the productivity of cells for ex vivo cell screening and expansion is a unique approach with numerous research and therapeutic uses.

Antibodies, Monoclonal↗

Short segment Barrett's oesophagus: prevalence, diagnosis and associations.

BACKGROUND: Prevalence of short segment Barrett's (SSB) oesophagus, defined as the absence of macroscopic Barrett's but histologically identifiable intestinal metaplasia, has been reported to be 18% based on haematoxylin and eosin (H&E) staining. AIMS: To define the prevalence of SSB oesophagus using H&E and alcian blue staining and to determine whether SSB oesophagus is associated with inflammation at the gastro-oesophageal junction (GOJ). SUBJECTS: Consecutive patients (n = 158) presenting for endoscopy completed a structured interview. METHODS: Two biopsy specimens taken from the GOJ were stained with H&E, alcian blue and Giemsa. A third specimen was obtained from the distal oesophagus. Intestinal metaplasia was diagnosed if goblet cells were definitely identified by two independent observers. RESULTS: SSB oesophagus was present in 46 (prevalence 36%, 95% confidence interval (CI) 28.5-43.5) using alcian blue staining. If H&E had been the sole staining method used, 50% cases of intestinal metaplasia would have been overlooked. There were no cases of intestinal metaplasia identified by H&E but missed by alcian blue staining. Logistic regression analysis identified age (odds ratio (OR) per decade 1.03, 95% CI 1.01-1.06), histological oesophagitis (OR 3.2, 95% CI 1.4-7.2) and inflammation at the gastrooesophageal junction (OR 5.9, 95% CI 2.2-15.6) as independent risk factors for SSB oesophagus. CONCLUSION: Unrecognised SSB oesophagus is highly prevalent in patients presenting for diagnostic upper endoscopy if alcian blue staining is applied.

Adult↗

[Unusual, unilateral metastasis of a prostate-carcinoma and palliative rhenium-186 pain-therapy].

A 82-year-old male patient had developed a suffering from an unusual unilateral growing bone metastases of a prostate-carcinoma D2 (Histological diagnosis: indifferent, partly cribiform growing prostate-carcinoma, T3N x M1, G3; first diagnosis 7/1988), which suggests a sufferring from M. Paget. In October 1988, the patient underwent a subcapsular orchiectomy, followed by androgene therapy with fugurel. Due to ongoing osseous metastases, in November/December 1992 a radiotherapy of the right hip (50 Gy) was performed. Beginning from October 1994, severe progression of bone metastases was observed with distinct pain-symptoms, leading to an increasing use of analgetics.

Aged, 80 and over↗

Amplification of the t(2; 13) and t(1; 13) translocations of alveolar rhabdomyosarcoma in small formalin-fixed biopsies using a modified reverse transcriptase polymerase chain reaction.

Detection of characteristic chromosomal translocations has aided diagnosis of the small round cell tumors of childhood and may help to stratify patients into clinical groups. The detection of the abnormalities by classical cytogenetic techniques has been supplemented by fluorescent in situ hybridization and reverse transcriptase polymerase chain reaction (RT-PCR). These techniques allow diagnoses to be made using only very small amounts of tumor tissue. We here describe a technique for the rapid and specific detection by modified reverse transcriptase polymerase chain reaction of characteristic chromosomal translocations of alveolar rhabdomyosarcoma with small amounts of formalin-fixed tissue as the starting material. Of 27 samples studied, 4 cases are described in which the detection of translocations by this method cast doubt on the original histopathological diagnosis. These cases demonstrate the critical diagnostic importance of the detection of these translocations in rhabdomyosarcoma.

Adolescent↗

[Pre- and intraoperative localization of neuroendocrine tumors].

Previous studies of the intraoperative use of a hand-held gamma probe to localize metastases and primary tumors of colorectal cancer have shown improved assessment of tumor spread and changes in surgical management based on added information gained by radioimmunoguided surgery. Following the injection of 180 MBq [111In-DTPA-D-Phe1]-pentetreotide and/or 500 MBq 99mTc-dimercaptosuccinic acid (both for dual-radionuclide scintigraphy) preoperative somatostatin receptor imaging [11 patients with GEP tumors] and dual-radionuclide scintigraphy. (8 patients with relapsing medullary thyroid carcinomas) was performed. One patient with a metastasizing pheochromocytoma underwent 123]-MIBg scintigraphy. Results were combined with the information obtained from conventional imaging modalities. Intraoperative radiodetection was performed 24 hours after administration of [111In-DTPA-D-Phe1]-pentetreotide or 4 hours following the injection of 99mTc(V)DMSA using a hand-held gamma probe (Tec Probe 2000. Stratec, FRG). Intraoperative gamma counting localized 39 somatostatin receptor positive lesions of GEP tumors whereas preoperative receptor imaging visualized 81%, surgical palpation 41% and radiological imaging modalities localized only 31%. In 8 patients with recurrent medullary thyroid carcinoma the surgeon was successful in localizing and removing 18 tumor lesions by the help of the gamma probe. Dual-radionuclide scintigraphy revealed 77% (Octreoscan 5/18; 99mTc-V-DMSA 9/18), surgical palpation 55% and conventional imaging methods (CT, sonography) only 38% of all lesions detected intraoperatively by the hand-held gamma probe. In summary, this preliminary data show that intraoperative hand-held gamma probe detection of microscopic and occult endocrine tumors is feasible and more sensitive than external scintigraphy and conventional imaging.

Adrenal Gland Neoplasms↗

Biological activity and therapeutic potential of homologs of an Ii peptide which regulates antigenic peptide binding to cell surface MHC class II molecules.

An invariant chain peptide (murine Ii76-92; Ii-Key) is known to produce a 10 to 50 times baseline enhancement of the presentation of specific antigenic peptides to murine T cell hybridomas by cell surface MHC class II molecules. In order to define structure-activity relationships in Ii-key, homologs were synthesized with the following systematic variations: 1) N- and C-terminal truncations, 2) N-terminal acetylation and C-terminal amidation, 3) substitutions with 13 natural amino acids in each position of the shortest, fully active peptide, and then with an additional 12 nonnatural amino acids at certain 'pharmacophore' positions, 4) substitutions with D-amino acids and N-methyl-leucine, and 5) cyclical forms. More than 160 homologs were tested for effects on antigen presentation by the murine MHC class II alleles: A(d), Ak, E(d), or Ek. For some compounds, allele specificity between E(d) and Ek exceeded 1:20. D-Amino acid and/or N-methyl-leucine substitutions were accepted at some residue positions, leading to peptides with relatively long half-lives in mouse serum and low toxicities in mice. An Ii-Key homolog inhibited in vitro presentation of an internally processed hen egg lysozyme determinant to a specific T hybridoma. The best compounds can be tested in vivo for therapeutic applications: 1) immunosuppression upon release of antigenic peptide, and 2) vaccination or immunomodulation upon co-administration of a second antigenic peptide.

Amino Acid Sequence↗

Serum relaxin and the major endometrial secretory proteins in in-vitro fertilization and down-regulated hormone-supported and natural cycle frozen embryo transfer.

Relaxin has been postulated to be a modulator of the expression of the endometrial secretory proteins, insulin-like growth factor binding protein (IGFBP-1) and placental protein 14 (PP14). This study evaluated the expression of relaxin in relation to concentrations of these secretory proteins along with oestradiol, progesterone and human chorionic gonadotrophin in groups of pregnant and non-pregnant patients who underwent differing assisted conception treatments. Serum samples were taken from 88 patients at 8 and 12 days after embryo transfer. At 12 days after embryo transfer, relaxin concentrations in the pregnant patients who had undergone in-vitro fertilization (IVF) or natural cycle frozen embryo transfer were significantly higher than those who did not conceive in these groups (mean concentrations 8334 versus 28 and 2608 versus 62 pg/ml respectively, P<0.001). However concentrations in the pregnant patients who had hormone support and transfer of frozen embryos were not significantly different from the patients who did not conceive after the same treatment. Although relaxin expression was associated with corpus luteum activity, it was not related to the number of corpora lutea in IVF patients. A wide range of relaxin concentrations was seen to be compatible with a healthy pregnancy. These serum relaxin concentrations were not found to be directly related to the serum concentrations of IGFBP-1, PP14 or the other factors assessed in this study.

Chorionic Gonadotropin↗

Caring for the pregnant woman with sickle cell crisis.

Pregnancy poses particular risks for women with sickle cell disease and their unborn babies. There is an increased risk of spontaneous abortion and preterm labour. Painful sickle cell crises tend to occur more frequently during pregnancy. A district-wide protocol for dealing with crises would help ensure the woman receives prompt, effective, knowledgeable care from GPs, midwives and A&E staff. Careful assessment is essential and hospital admission is usually required. Adequate relief of pain, and sometimes blood transfusions, are the cornerstones of treatment. Health education plays a part in prevention of crises. Care could be improved by more specialist centres and specialist nurses or midwives.

Acute Disease↗

Altered target organ. A mechanism of postrecovery resistance to murine autoimmune oophoritis.

Experimental murine autoimmune oophoritis, a model of human premature ovarian failure, is induced by immunization with a peptide of the ZP3 glycoprotein from mouse zona pellucida (ZP3(330-340)) in CFA. The ovarian pathology is mediated by ZP3-specific, CD4+ T cells, and not by Abs. We now show that mice recovered from autoimmune oophoritis in 4 mo, as characterized by regression of ovarian inflammation. Recovery was associated with disease resistance upon rechallenge with ZP3(330-340) in CFA. Oophoritis resistance was not explicable by immunosuppressive effect of CFA priming, nor by suppression of pathogenic T cells. ZP3-specific, proliferative T cell response could be detected, and a ZP3-specific, IFN-gamma-producing pathogenic T cell line was derived readily from the recovered mice by in vitro stimulation with the ZP3(330-340) peptide. Moreover, recovered mice, when challenged with ZP3(330-340) in CFA, produced Abs of IgG class to the ZP3(330-340) peptide. Suppressor T cells are not readily demonstrable. Most importantly, oophoritis occurred in normal ovaries implanted under the renal capsule of the recovered mice. That oophoritis developed in the implanted ovaries, but spared the endogenous ovaries, further indicates that the latter is refractory to oophoritis. Disease resistance of the ovaries is not explicable by limitation of accessible target Ags. When mated, recovered mice were fertile and produced normal litters; and, as recipients of a ZP3-specific T cell line, their ovaries developed oophoritis. We conclude that altered local environment of the target organ following autoimmune disease recovery can contribute to the complex disease-resistant state.

Animals↗

[Systemic infection due to group A Streptococcus pyogenes].

A 47-year-old woman developed oedematous swelling of the skin over the left hip and leg, with joint pains and reddening over joints of the hands and left ankle. 2 months before her son had had scarlet fever, following which the patient had two episodes of fever. Shortly before hospitalization she was treated with a glucocorticoid because a rheumatic disease had been suspected. On admission the blood sedimentation rate was 58/90, the white cell count was 15.100/microliters with left shift in the differential count. The swellings in arms and legs became abscesses which were incised. An abscess over the left buttock, diagnosed by 67-gallium whole-body scintigraphy, was also treated surgically. On the day of admission penicillin (10 mill. IU three times daily intravenously) and, from the 4th day onwards, gentamicin (80 mg three times daily intravenously) were administered. Histological examination of fascia and muscle biopsies revealed nonspecific inflammation without signs of malignancy, white blood culture grew group A Streptococcus pyogenes. 20 days after the surgical intervention the patient was discharged in full health. Necrotizing fasciitis caused by Streptococcus pyogenes has become more frequent in the last few years and has often been accompanied by severe systemic complications.

Fasciitis↗

Invariant chain peptides enhancing or inhibiting the presentation of antigenic peptides by major histocompatibility complex class II molecules.

Two soluble invariant chain (Ii) peptides with overlapping sequences had contrasting effects on the presentation of antigenic peptides by murine Ad, Ak, Ed, and Ek major histocompatibility complex (MHC) class II molecules. Naturally produced class II-associated invariant chain peptides human (h)Ii81-104/murine (m)Ii80-103 inhibited antigen presentation on these MHC class II alleles in a manner consistent with competitive inhibition. The Ii-4 peptides hIi77-92/mIi76-91 enhanced presentation of antigenic peptides on I-E class II alleles by promoting the exchange of peptides at the cell surface. Treatment of antigen-presenting cells (APC) with Ii-4 before the addition of antigenic peptide greatly enhanced subsequent T cell responses, while treatment of APC with Ii-4 after antigenic peptide binding decreased subsequent T cell responses. The hIi81-104 and mIi80-103 peptides inhibited T cell responses in both types of assays. The binding of biotinylated antigenic peptide to MHC class II-transfected L cells, as measured by flow cytometry, was inhibited by mIi80-103 and enhanced by mIi-4. Segments of Ii fragments remaining associated with MHC class II, or released Ii peptides, appear to regulate the formation of stable antigenic peptide/MHC class II complexes either positively or negatively through interactions at or near the antigenic peptide binding site. These findings open a pathway for the design of novel therapeutics based on the structure and function of natural and rationally designed fragments of Ii.

Amino Acid Sequence↗