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Biomedical subjects

R Decker

Publications and source records attributed to R Decker.

At least 19 recordsLinked to original sources

Low seroprevalence of HTLV-I and HTLV-II in patients with a sexually transmitted disease. Study Group for HTLV and STDs.

To determine the prevalence of HTLV I-II among highly sexually active adults, a seroprevalence study was conducted in Italy between March 1992 and March 1993 among 1506 patients with a newly diagnosed STD. Individuals were tested with an enzyme immunoassay that employs a double viral lysate from HTLV-I and HTLV-II infected cell lines; confirmation and discrimination between HTLV-I and II were performed by a dot-blot immunoassay. One patient (0.07%) was confirmed HTLV-I positive and one (0.07%) HTLV-II positive. The HTLV-I positive was a Romanian woman, and the other was an intravenous drug user. The 0.13% HTLV prevalence observed in this study is intermediate between the 0.034% found among Italian blood donors and the 3.5-6% found among Italian intravenous drug users. These data suggest that there is not a high prevalence of these viruses among Italians with STDs.

Adult↗

Distribution of cyclosporin A in ocular tissues after topical administration to albino rabbits and beagle dogs.

PURPOSE: To determine the ocular pharmacokinetics of cyclosporin A after topical ophthalmic administration. METHODS: Radiolabled cyclosporin A in either a castor oil-in-water emulsion or a corn oil ointment was applied to the eyes of beagle dogs or albino rabbits using the following paradigms: (i) single doses of 0.2% emulsion to rabbits and dogs, (ii) single doses of 0.05%, 0.2%, or 0.4% emulsion to rabbits, (iii) multiple doses of 0.2% emulsion to dogs, (iv) single and multiple doses of 0.2% ointment to rabbits. The distribution of cyclosporin A was determined by measuring the distribution of radioactivity. RESULTS: After a single dose, cyclosporin A was rapidly absorbed into the conjunctiva (Cmax: dogs, 1490 ng/g; rabbits, 1340 ng/g) and cornea (Cmax: dogs, 311 ng/g; rabbits, 955 ng/g). High concentrations (>300 ng/g) could be detected in the cornea up to 96 hours post-dose. Lower concentrations were found in the intraocular tissues, and systemic absorption was minimal. After multiple doses, there was some accumulation in the cornea, lens, lacrimal gland, and iris-cilliary body, but limited accumulation in the conjunctiva and sclera. Ocular tissue concentrations of cyclosporin A increased with increasing dose concentration; proportionally in lacrimal gland and intraocular tissues; less than proportionally in conjunctiva and cornea. The pharmacokinetic profile of the cyclosporin A corn oil ointment was similar to that of the emulsion. CONCLUSIONS: Topical ophthalmic cyclosporin A penetrated into extraocular tissues at concentrations adequate for local immunomodulation while penetration into intraocular tissues was much less and absorption into the blood was minimal.

Absorption↗

New-onset psychogenic seizures after surgery for epilepsy.

BACKGROUND: The emergence of psychogenic seizures after surgery for epilepsy is not well recognized. OBJECTIVES: To identify the frequency of psychogenic seizures in an 11-year surgical experience and to characterize the patients with this complication. METHODS: Ninety-six patients underwent surgery for epilepsy between 1985 and 1996. The surgical database was reviewed and all patients who experienced postoperative psychogenic seizures were identified. Patients were characterized by sex, age, psychopathologic conditions, full-scale IQ, duration of epilepsy, surgical procedure, and operative complications. Patients were compared with the surgical group as a whole for these variables. SETTING: A comprehensive epilepsy center. RESULTS: Five patients were identified: 3 men and 2 women. Mean full-scale IQ was 73 (range, 66-82). Mean age was 29.8 years (range, 22-36 years). Three patients were diagnosed as having psychosis, 1 with borderline personality disorder and 1 with generalized anxiety. Operations included 4 anterior temporal lobectomies and 1 occipital lobectomy. Two patients experienced operative complications. Compared with the surgical cohort, patients had a higher frequency of preoperative psychopathologic conditions, lower mean full-scale IQ, and a greater occurrence of operative complications. CONCLUSIONS: (1) Patients can develop new-onset psychogenic seizures after surgery for epilepsy. (2) Low full-scale IQ, serious preoperative psychopathologic conditions, and major surgical complications may be risk factors. (3) Atypical postoperative seizures should be evaluated with video electroencephalographic monitoring before concluding that they are epileptic.

Adult↗

Comparison of laparoscopic and open staging in Hodgkin disease.

BACKGROUND: Staging laparotomy provides useful information for management of Hodgkin disease but has fallen into disfavor because procedure-related morbidity exceeds that of new chemotherapeutic regimens. OBJECTIVE: To determine the feasibility, effectiveness, and safety of laparoscopic staging for Hodgkin disease compared with those of open staging. PATIENTS: Fifty-five patients with Hodgkin disease of cell types including nodular sclerosis in 43 (78%), mixed cellularity in 9 (16%), and lymphocyte predominance in 3 (5%). STUDY DESIGN: Concurrent evaluation of laparoscopic staging (n = 15) and retrospective review of open staging (n = 40). INTERVENTIONS: Laparoscopic and open techniques of surgical staging for Hodgkin disease, including splenectomy, liver biopsies, and lymph node sampling. MAIN OUTCOME MEASURES: Operative time, duration of postoperative ileus and of postoperative hospitalization, morbidity, number of lymph nodes retrieved, alteration in pathologic stage, recurrence, and survival. RESULTS: For laparoscopic staging vs open staging groups, mean operative time was 202 vs 144 minutes (P=.001); mean postoperative ileus was 1.9 vs 3.2 days (P<.001); mean postoperative hospitalization was 4.4 vs 6.7 days (P<.001); complications occurred in 3 patients (20%) vs 11 patients (28%) (P=.57); and mean number of lymph nodes retrieved was 8.5 vs 4.6 (P=.05). In the laparoscopic staging group, 2 cases (13%) were upstaged and 2 cases (13%) were downstaged. In the open staging group, 6 cases (15%) were upstaged and 3 cases (7.5%) were downstaged. Follow-up data were available for all patients in the laparoscopic staging group, at a mean of 23.5 months postoperatively. All were alive, none had recurrent disease below the diaphragm, and 2 (13%) had residual mediastinal disease. Follow-up data were available for 31 patients (78%) in the open staging group at a mean of 52.5 months postoperatively. All were alive, 27 (87%) were disease free, 3 (10%) had had relapses above the diaphragm, and 1 (3%) had residual mediastinal disease. CONCLUSIONS: Compared with open staging, laparoscopic staging of Hodgkin disease is oncologically equivalent and functionally superior. These data should encourage reappraisal of the role of operative staging in the management of Hodgkin disease.

Adolescent↗

The prevalence of surface antigen variants of hepatitis B virus in Papua New Guinea, South Africa, and Sardinia.

Three assays, one based on monoclonal antibodies and the others on polyclonal antibodies, were employed to detect hepatitis B surface antigen (HBsAg)-reactive samples in both vaccinated and unvaccinated populations in areas of the world where hepatitis B virus (HBV) is endemic. Any discordant sera were tested by polymerase chain reaction (PCR) to confirm current infection, and sequence data were obtained from the DNA coding for the major hydrophilic region (MHR) of HBsAg of those samples positive for PCR. In all countries studied, samples that reacted in one HBsAg assay but not another were found. In the most extreme case, about 5% of viremic sera in Papua New Guinea were nonreactive in the monoclonal HBsAg assay; 9 of the 13 PCR-positive samples had novel or once-described variants, or a variant out of its usual genotype context. In South Africa, samples with sequences of subtype ayw2 reacted poorly, particularly in the polyclonal assay. Two had novel variants. In Sardinia, antibody to hepatitis B core antigen (anti-HBc) was analyzed as a marker of infection. A significant proportion of anti-HBc-positive, but monoclonal HBsAg-negative, vaccinees and unvaccinated persons were found to be PCR positive, as were some individuals without any markers of hepatitis B virus infection. Five more novel variants were found in these groups. There are implications for the design of HBsAg assays, which may have to be modified according to local sequence variability. Not all discordant samples were explained by variants, indicating that assay sensitivity is fundamental to diagnostic efficacy. Overall, this study defined 16 novel variants and 2 new potential epitope clusters.

Amino Acid Sequence↗

Search for retrovirus in patients with multiple sclerosis.

Multiple sclerosis (MS) patient samples were screened for known or novel retroviruses using an ultrasensitive technique, IMx PERT, that detects the presence of reverse transcriptase (RT). This procedure has 10(5)- to 10(7)-fold greater sensitivity than conventional RT assays and is capable of detecting 10 to 50 virions. Moreover, IMx PERT is at least as sensitive as polymerase chain reaction, and requires no previous knowledge of viral nucleotide sequence. The MS specimens analyzed in this study included 136 sera from 79 patients and 128 cerebrospinal fluid samples from 53 patients with relapsing or chronic progressive disease. In addition, peripheral blood mononuclear cells from 19 MS patients were cultured in an attempt to amplify or induce expression of low-copy number or cell-associated retrovirus. No evidence of retrovirus was found in any of the specimens obtained from MS patients.

Base Sequence↗

Angiotensin II and basic fibroblast growth factor induce neonatal bladder stromal cell mitogenesis.

PURPOSE: Our aims were to establish primary stromal cell cultures from the neonatal rabbit bladder and investigate the potential mitogenic effects of angiotensin II and basic fibroblast growth factor on these cells. MATERIALS AND METHODS: Primary bladder stromal cell cultures were obtained from 3-day-old rabbits, plated at a density of 3 x 10(4) cells per ml. and allowed to grow for 24 hours. Subconfluent cells were growth arrested in serum deficient (0.25% newborn calf serum) or serum-free media for 24 hours and then stimulated with 10(-7) M. angiotensin II or 10 ng./ml. basic fibroblast growth factor for an additional 48 hours. Cell counts and [3H] thymidine incorporation were done to measure cellular proliferation and deoxyribonucleic acid synthesis. RESULTS: Angiotensin II and basic fibroblast growth factor each stimulated neonatal bladder stromal cell proliferation and [3H] thymidine incorporation under serum deficient conditions. Angiotensin II provoked an average 26% increase in cell number (p < 0.01) and 35% increase in [3H] thymidine incorporation (p < 0.01) compared to control values. Basic fibroblast growth factor was an even more potent mitogen with a 47% increase in cell number (p < 0.01) and 180% increase in [3H] thymidine incorporation (p < 0.01) compared to controls. In contrast, angiotensin II and basic fibroblast growth factor each failed to have significant stimulatory effects under serum-free conditions. CONCLUSIONS: Angiotensin II and basic fibroblast growth factor induce a mitogenic response to neonatal bladder stromal cells in vitro. These mitogenic effects require the presence of serum factors. Whether angiotensin II and basic fibroblast growth factor are involved in the in vivo regulation of bladder growth associated with obstructive uropathy requires further investigation.

Angiotensin II↗

Fulminant reactivation of hepatitis B due to envelope protein mutant that escaped detection by monoclonal HBsAg ELISA.

The detection of a fatal case of reactivation of hepatitis B, in a previously vaccinated Indonesian patient after withdrawal of chemotherapy for lymphoma, was delayed because HBsAg was negative in a widely used monoclonal-antibody-based ELISA. The serum was later found to be strongly reactive for HBsAg by the polyclonal radioimmunoassay and for HBV DNA. PCR sequencing revealed a substitution of arginine for glycine at position 145 of HBsAg in the major neutralising epitope cluster, the a determinant, as well as a 2-aminoacid insertion of asparagine and threonine between positions 122 and 123, immediately upstream of this determinant.

Amino Acid Sequence↗

Effect of stress on amino acids and related compounds in various tissues of the rat.

The composition of various amino acids and related compounds in the aorta, ventricle, atria, liver, kidney, pancreas, bronchi and adrenals of rats is presented. These patterns are qualitatively similar, but quantitatively different. Stress changed these patterns. In the aorta, alpha-aminobutyric acid and ammonia are decreased. In the ventricle, phosphoserine and red. Glutathione are increased; and ammonia, arginine, asparagine, carnosine, ethanolamine, glutamic acid, glutamine, lysine, phosphoethanolamine and taurine are decreased. In the atria, alpha-aminobutyric acid, aspartic acid, ethanolamine and red. glutathione are increased; and ammonia is decreased. In the liver, alpha-aminobutyric acid, cystine, isoleucine, red. glutathione, methionine and phenylalanine are increased. In the kidney, ethanolamine is increased; and beta - aminobutyric acid, citrulline, cystathionine, glutamic acid, glycine and tryptophan are decreased. In the pancreas, alpha-aminoadipic acid, ox. glutathione, leucine, glutamine, 1-methylhistidine, phenylalanine, phosphoserine, tryptophan and valine are increased; and ammonia, cystine and aspartic acid are decreased. In the adrenal glands, anserine, glutamic acid, glutamine and ox. glutathione are increased; and arginine is decreased. In the bronchi, ethanolamine and beta-alanine are increased and alpha-aminobutyric acid and ox. glutathione are decreased. Thus, stress affects certain amino compounds but changes are substance and tissue specific and independent of changes seen in the plasma.

Amino Acids↗

Evaluation of the circle of Willis with three-dimensional CT angiography in patients with suspected intracranial aneurysms.

PURPOSE: To determine the usefulness of CT angiography in the setting of suspected acute subarachnoid hemorrhage or intracranial aneurysm. METHODS: We prospectively studied 68 patients suspected of having subarachnoid hemorrhage or an intracranial aneurysm with noncontrast CT of the head followed immediately by contrast-enhanced helical CT of the circle of Willis with three-dimensional reconstruction. Twenty-seven patients with CT findings positive for subarachnoid hemorrhage or intracranial aneurysm were evaluated with digital subtraction angiography or MR angiography within 12 hours of CT angiography. Patients with negative CT/CT angiography findings were followed up with lumbar puncture. RESULTS: CT angiography showed 23 of 24 aneurysms and 2 of 2 arteriovenous malformations (sensitivity, 96%; specificity, 100%). Aneurysm size ranged from 2 to 40 mm (mean, 7.9 mm). Interobserver variability was 10%. In the 23 cases of subarachnoid hemorrhage, cisternal blood did not limit the three-dimensional reconstruction. Two patients with aneurysms on CT angiography had normal noncontrast scans. CONCLUSIONS: CT angiography of the circle of Willis is a useful technique for evaluation of suspected acute subarachnoid hemorrhage and intracranial aneurysm. It provides anatomic display of intracranial aneurysms, allowing for planning of conventional angiography and surgical approach. In selected cases, CT angiography may eliminate the need for preoperative conventional angiography.

Adolescent↗

O6-methylguanine-DNA methyltransferase in human brain tumors detected by activity assay and monoclonal antibodies.

O6-methylguanine-DNA methyltransferase (MGMT) activity was measured in 68 tissue samples taken from brain. A wide range in activity among samples was observed, with all nonmalignant samples showing transferase activity (Mer+) but approximately 15% of WHO grade II low-grade astrocytomas and WHO grade IV glioblastoma multiformes lacking activity (Mer-). On average, astrocytomas and glioblastomas showed less transferase activity than either nonmalignant tissue or meningiomas. Monoclonal antibodies specific for MGMT showed both cytoplasmic and nuclear staining of Mer+ brain tumor cells in culture but no staining of Mer- cells in culture. In pathology specimens from anaplastic astrocytomas, glioblastoma multiformes, and meningiomas, antibody staining revealed both cytoplasmic and nuclear MGMT, while one sample showed little or no MGMT-specific staining. These results help explain why nitrosoureas have been among the most successful agents in treatment of brain tumors and indicate the subcellular localization for the repair activity, which may be relevant to nitrosourea resistance.

Antibodies, Monoclonal↗

Plasma natriuretic factor(s) in patients with intracranial disease, renal salt wasting and hyperuricosuria.

To test our hypothesis that a circulating factor(s) may be causing the renal salt and urate wasting in patients (pts) with intracranial diseases, we exposed rats to the plasma of these patients and studied sodium and lithium transport. We selected 21 neurosurgical pts, 13 of whom had increased fractional excretion (FE) of urate, and 14 age and sex-matched controls. Plasma from pts and controls were injected IP (0.5 mL) and infused, 0.2 ml prime and 1.8 mL at 0.01 mL/min, to Sprague Dawley rats anesthetized with Inactin. Renal transport of sodium (Na), lithium (Li) and potassium (K) was determined. There were higher mean +/- SEM for FENa, 0.59 +/- 0.07% vs 0.29 +/- 0.05%, P < 0.01, FELi, 36.6 +/- 1.9% vs 24.0 +/- 1.6%, P < 0.001 and K excretion rates, 1.69 +/- 0.13 vs 1.31 +/- 0.09 mumol/min, p < 0.02, in rats infused with plasma of pts as compared to controls, respectively. FENa decreased with increasing dilution of plasma of 2 pts with ICD. There was no difference in mean weight of rats, blood pressure, urine flow rate or insulin clearance between pts and controls. These data suggest that pts with ICD have a plasma factor(s) which decreases net Na, Li and K reabsorption.

Adult↗

Detection of messenger RNA from O6-methylguanine-DNA methyltransferase gene MGMT in human normal and tumor tissues.

BACKGROUND: The level of the DNA repair protein O6-methylguanine-DNA methyltransferase is an important determinant of the response of tumor cells in culture to alkylating nitrosoureas. In these cells, the abundance of messenger RNA (mRNA) is directly correlated with repair activity. PURPOSE: Our purpose was to compare transferase mRNA levels with the repair activity in primary human tumors. METHODS: Human transferase mRNA was measured in tissue samples from brain tumors, normal lung, lung tumors, ovarian tumors, and normal human liver by use of an RNA protection assay with an antisense probe prepared from the cloned gene. RESULTS: Normal and tumor tissue samples from the same patient had similar transferase activity levels, but transferase expression varied widely among tissue samples from different patients. Brain and lung samples, on average, had transferase mRNA levels closer to those in liver samples than their transferase activity levels. In two cases, tissue samples which were transferase deficient by the activity assays were found to lack transferase mRNA. CONCLUSIONS: Deficiencies in transferase activity are due to reduced or absent mRNA transcription or processing. In brain and lung, there may be post-transcriptional control of mRNA expression. The wide interindividual variation in transferase expression is also seen at the transcription level. IMPLICATIONS: These are among the first measures of transferase mRNA expression in primary human tissue. More samples should be examined to extend these observations.

Brain Neoplasms↗

Anti-GOR and hepatitis C virus in autoimmune liver diseases.

Anti-GOR is an autoantibody found in hepatitis C virus (HCV) infection. We have studied the specificity of this antibody for HCV infection in various groups of autoimmune liver diseases. Anti-HCV was detected by a second generation HCV enzyme-linked immunosorbent assay in 14 of 29 patients with liver-kidney-microsomal (LKM-1) -antibody-positive autoimmune hepatitis type 2 and in all 6 control patients with HCV-RNA-positive chronic hepatitis C. Anti-HCV was not found in those with antinuclear-antibody-positive autoimmune hepatitis type 1 (10 patients), with soluble-liver-protein-antibody-positive autoimmune hepatitis type 3 (8), with primary biliary cirrhosis (9), with systemic lupus erythematosus (SLE) (10), or in healthy controls (13). Anti-GOR was detected in 11 of 14 patients with autoimmune hepatitis type 2 who were all positive for anti-HCV but only in 1 of 15 LKM-1 patients who were negative for anti-HCV. We did not find anti-GOR in any other group of autoimmune liver disease, SLE, or control sera, but this antibody was detected in 3 of 6 patients with chronic hepatitis C. Autoimmune hepatitis type 2 patients who were anti-GOR positive and anti-HCV positive were less likely to be female, were older (p less than 0.001), and had lower LKM-1 antibody titres (p less than 0.001), lower disease activity, and responded less effectively to immuno- suppression than did those who were anti-HCV negative/anti-GOR negative. The findings show that anti-GOR reflects HCV-specific autoimmunity. HCV seems to induce autoimmunity to both GOR (an HCV-specific autoepitope) and LKM-1 (an epitope that is also recognised by autoimmune hepatitis sera of a different cause). Anti-GOR and LKM-1 antibodies contribute to a better differentiation of chronic hepatitis, a finding that has therapeutic implications.

Adolescent↗