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T Sheehan

Publications and source records attributed to T Sheehan.

At least 19 recordsLinked to original sources
PubMed2001

Evidence that the medial amygdala projects to the anterior/ventromedial hypothalamic nuclei to inhibit maternal behavior in rats.

The maternal behaviors shown by a rat that has given birth are not shown by a virgin female rat when she is first presented with young. This absence of maternal behavior in virgins has been attributed to the activity of a neural circuit that inhibits maternal behavior in nulliparae. The medial amygdala and regions of the medial hypothalamus such as the anterior and ventromedial hypothalamic nuclei have previously been shown to inhibit maternal behavior, in that lesions to these regions promote maternal responding. Furthermore, we have recently shown that these and other regions, such as the principal bed nucleus of the stria terminalis, the ventral lateral septum, and the dorsal premammillary nucleus, show higher pup-induced Fos-immunoreactivity in non-maternal rats exposed to pups than during the performance of maternal behavior, indicating that they too could be involved in preventing maternal responsiveness. The current study tested whether the medial amygdala projects to the anterior/ventromedial hypothalamic nuclei in a neural circuit that inhibits maternal behavior, as well as to see what other brain regions could participate in this circuit. Bilateral excitotoxic lesions of the medial amygdala, or of the anterior/ventromedial hypothalamic nuclei, promoted maternal behavior. Unilateral medial amygdala lesions caused a reduction of pup-induced Fos-immunoreactivity in the anterior/ventromedial hypothalamic nuclei in non-maternal rats ipsilateral to the lesion, as well as in the principal bed nucleus of the stria terminalis, ventral lateral septum, and dorsal premammillary nucleus. Finally, unilateral medial amygdala lesions paired with contralateral anterior/ventromedial hypothalamic nuclei lesions promoted maternal behavior, although ipsilateral lesion placements were also effective.Together, these results indicate that the medial amygdala projects to the anterior/ventromedial hypothalamic nuclei in a neural circuit that inhibits maternal behavior, and that the principal bed nucleus of the stria terminalis, ventral lateral septum, and dorsal premammillary nucleus could also be involved in this circuit.

Amygdala↗
PubMed2000

Safety assessment of iron EDTA [sodium iron (Fe(3+)) ethylenediaminetetraacetic acid]: summary of toxicological, fortification and exposure data.

Iron EDTA [sodium iron (Fe(3+)) ethylenediaminetetraacetic acid (EDTA)], shown to have a significant beneficial effect on iron status by increasing iron bioavailability in human diets, has been proposed for use as a fortificant in certain grain-based products including breakfast cereals and cereal bars. This paper presents an assessment of the safety of iron EDTA for its intended uses in these products. Iron EDTA, like other EDTA-metal complexes, dissociates in the gastrointestinal tract to form iron, which is bioavailable, and an EDTA salt; absorption of the metal ion and EDTA are independent. Because of this dissociation, consideration of information on EDTA compounds other than iron EDTA is relevant to this safety assessment. EDTA compounds are poorly absorbed in the gastrointestinal tract and do not undergo significant metabolic conversion. They have a low degree of acute oral toxicity. EDTA compounds are not reproductive or developmental toxicants when fed with a nutrient-sufficient diet or minimal diets supplemented with zinc. In chronic toxicity studies, diets containing as much as 5% EDTA were without adverse effects. EDTA compounds were not carcinogenic in experimental animal bioassays and are not directly genotoxic. This lack of significant toxicity is consistent with a history of safe use of other EDTA compounds (CaNa(2)EDTA and Na(2)EDTA) approved by the FDA for use as direct food additives. An upper-bound estimated daily intake (EDI) of EDTA from iron EDTA (1.15mg/kg bw/day for the US population) is less than half the acceptable daily intake (ADI) for EDTA of 2. 5mg/kg bw/day established by JECFA. The data collected and published over the past 20 to 30 years demonstrate that iron EDTA is safe and effective for iron fortification of food products and meets the standard of "reasonable certainty of no harm". Based on the published record, iron EDTA may be regarded as generally recognized as safe (GRAS) for the intended food uses and maximum use levels.

Animals↗
PubMed1994

Lorazepam-enhancement of the antiemetic efficacy of dexamethasone and promethazine. A placebo-controlled study.

This investigation was designed with the objective of improving on currently available antiemetic regimens to counteract the disabling side effects of cancer chemotherapy. The combination of lorazepam, dexamethasone, and promethazine was compared with dexamethasone and promethazine without lorazepam in a double-blind crossover study. The initial study population consisted of 92 women (most with breast cancer) and 7 men; all received moderately or highly emetogenic chemotherapy. Complete data for both periods of therapy were available for 73 of these patients. Crossover analysis showed a highly significant effect of lorazepam in reducing the severity of nausea (p = .003); the severity of vomiting was also reduced, but less dramatically (p = .051). The frequency of all degrees of nausea and vomiting was less with lorazepam, but the difference was not statistically significant. It is concluded that lorazepam added to dexamethasone and promethazine provides an effective regimen for counteracting the emetic side effects of cancer chemotherapy.

Adult↗
PubMed1993

Chiral separation and detection enhancement of propranolol using automated pre-column derivatization.

In the liquid chromatographic analysis of pharmaceuticals, two challenges are often encountered: detectivity and chiral separations. Propranolol, a beta adrenergic blocker, is a pharmaceutical compound that faces both of these limitations. In this study, both limitations are overcome simultaneously using derivatization with (+)-1-(9-fluorenyl)ethyl chloroformate (FLEC), a highly fluorescent and chiral reagent. The derivatization is automated using an autosampler with an AutoMix microrobotic feature, which greatly contributes to the efficiency and reproducibility of the method when manipulating microliter volumes of sample and reagents. The method yields excellent separation of the diasteriomers, has a detection limit of 1 picomol, good reproducibility and linearity in the 50-400 pmol range (on column). In addition, this method is simple, requires no elevated temperature, no chiral stationary or mobile phases and can be easily automated.

Chromatography, High Pressure Liquid↗
PubMed1993

Matrix effects in the derivatization of amino acids with naphthalene dicarboxaldehyde, 9-fluorenylmethyl chloroformate and phenylisothiocyanate.

Pre-column derivatizations of amino acids often present two major challenges: 1) automation, due to the multi-step manipulations for pH control, reagent addition, mixing and extraction, and 2) effect of matrices in the sample such as salts, buffers and surfactants. Both issues have been addressed in a previous publication on derivatization methods using 9-fluorenylmethyl chloroformate (FMOC) and phenylisothiocyanate (PITC). In this paper, a third method of derivatization, which has recently been developed and published, was studied to address the same issues. The derivatization reagent, naphthalene-2,3-dicarboxaldehyde (NDA), is a modification from o-phthalaldehyde (OPA) and yields more stable derivatives with high fluorescence efficiencies. An autosampler was programmed to mix amino acid samples with cyanide and NDA reagent, allow a programmed reaction time and finally inject onto the HPLC. To study sample matrix effects, amino acid samples were spiked with various concentrations of Tris-HCl, phenol, citrate, sulfosalicylic acid, sodium chloride and sodium dodecyl sulfate. The recoveries of amino acids in varied sample matrices were compared to pure amino acid standards. The matrix effects using the NDA method were similar to those using the FMOC method. Comparisons of all three methods (NDA, FMOC and PITC) are discussed and tabulated.

Amino Acids↗
PubMed1992

Enhancement of detection sensitivity and cleanup selectivity for tobramycin through pre-column derivatization.

Reversed-phase high-performance liquid chromatography, UV detection and reversed-phase solid-phase extraction (SPE) as analytical methods for pharmaceutical compounds face a challenge when the compound is rather polar and lack UV absorptivity. A good example is tobramycin. To overcome these problems, a method has been developed using pre-column derivatization of tobramycin with o-phthalaldehyde and automated with an autosampler with microrobotic routines. The detection enhancement of the derivatives was achieved by using fluorescence detection which was forty times more sensitive than using UV detection. Recovery studies of standards and spiked serum samples show that pre-SPE derivatization significantly enhances the recoveries (by at least a factor of 3) and the quality of cleanup over post-SPE derivatization.

Chromatography, High Pressure Liquid↗
PubMed1991

An unusual case of amyloidosis complicating light chain myeloma.

We present an unusual case of light chain myeloma complicated by systemic amyloidosis. There was massive infiltration of the left iliopsoas and quadratus femoris muscles with amyloid, manifesting itself clinically as a progressive, painless limp. We point out that accurate diagnosis by muscle biopsy in such cases has important prognostic implications and may avoid the unnecessary use of potentially toxic and ineffective treatment.

Aged↗
PubMed1991

Matrix effects in the derivatization of amino acids with 9-fluorenylmethyl chloroformate and phenylisothiocyanate.

Pre-column derivatization of amino acids is widely practiced today for the HPLC analysis of amino acids. Due to the requirement for pH control, excess reagent removal and multi-step manipulations, automation is a major challenge in the derivatization of amino acids. Another challenge for pre-column chemistries is the effect of matrices in the sample such as salts, buffers and surfactants. This paper reports on automated derivatization using phenylisothiocyanate (PITC) and compares matrix effects between this PITC method and that of derivatization using 9-fluorenylmethyl chloroformate (FMOC). An autosampler was programmed to mix amino acid samples with PITC or FMOC reagent, allow a programmed reaction time, extract excess reagent and finally inject onto the HPLC. To study sample matrix effects, amino acid samples were spiked with various concentrations of Tris-HCl, phenol, citrate, sulfosalicylic acid, sodium chloride and sodium dodecyl sulfate. Using the PITC method and the FMOC method, the recoveries of amino acids in varied sample matrices were compared to pure amino acid standards. The PITC method appears to be affected less by matrix effects than the FMOC method. However, the FMOC method has a higher sensitivity so that sample dilution (up to 30 times) can be used to eliminate matrix effects.

Amino Acids↗
PubMed1989

Prognostic significance of activation and differentiation antigen expression in B-cell non-Hodgkin's lymphoma.

Immunophenotyping shows heterogeneity of expression of activation and differentiation antigens in B-cell non-Hodgkin's lymphoma (NHL). To investigate whether antigen expression correlates with clinical behaviour we have studied the clinical presentation and follow-up of a series of 111 B-cell lymphomas previously phenotyped for a panel of antigens including CD groups 5, 9, 10, 21, 23, 25, 30, 38, 4F2 antigen, and transferrin receptor. CD antigens 5, 10, and 23 were expressed significantly more often by low grade lymphomas whereas CD38, 4F2 antigen, and transferrin receptor were more often expressed by high grade lymphomas. There was a significant correlation with survival and age, stage at presentation, histological grade, and expression of 4F2 antigen and transferrin receptor but not with the other antigens studied. 4F2 antigen and transferrin receptor may identify a poor prognostic group of cases in low grade lymphoma but we conclude that phenotyping B-cell NHL for many of the antigens expressed at various stages of B-cell differentiation and activation does not provide clinically useful information in addition to that obtained from standard histological classifications.

Antigens, CD↗
PubMed1989

Central nervous system involvement in haematological malignancies.

We have reviewed our experience of central nervous system (CNS) involvement in 540 patients with lymphoma or acute leukaemia treated at the Royal Infirmary of Edinburgh between 1979 and 1987. CNS invasion is a significant problem in acute lymphoblastic leukaemia but may well respond to treatment, while in acute non-lymphoblastic leukaemia this complication occurs too infrequently to justify routine CNS prophylaxis. CNS involvement in Hodgkin's disease or non-Hodgkin's lymphoma (NHL) of low-grade malignancy was uncommon, exclusively of the extradural variety, and did not appear to alter the ultimate prognosis. Diffuse leptomeningeal involvement occurred with significant frequency in more aggressive NHL, often while the disease was in systemic remission or during remission induction. The prognosis for leptomeningeal disease or intracranial mass lesions was extremely poor and some form of CNS prophylaxis may be justified in aggressive NHL.

Acute Disease↗
PubMed1988

T-cell lymphoma: morphology, immunophenotype and clinical features.

The histology, immunophenotype and clinical presentation of 43 cases of T-cell lymphoma are described. Cases were classified into nine types; T-lymphocytic lymphoma (three), mycosis fungoides (six), Sézary syndrome (two), T-zone lymphoma (13), angioimmunoblastic lymphadenopathy (AIL)-like T-cell lymphoma (five), pleomorphic medium cell (one), large cell immunoblastic (four), large cell polylobated (five) and lymphoblastic (four). The patients comprised 26 males and 17 females aged between 15 and 86 years. The majority showed disseminated disease at the time of diagnosis (18 stage IV, nine stage III, five stage II, eight stage I and three cases not staged). Thirty-one patients showed lymph node involvement. Cutaneous involvement was a common finding (18 cases, 10 cases excluding mycosis fungoides and Sézary syndrome). Details of therapy and clinical follow-up were obtained in 37 cases. With simple chemotherapy only one complete response (7%, 1/16) was obtained. With aggressive therapy 48% (13/27) of patients showed complete responses. Twenty patients died during the follow-up period. Life table analysis showed a 58% probability of surviving 1 year and 36% probability of surviving 3 years. There was a significant difference in survival probability between low/intermediate-grade (lymphocytic, Sézary syndrome, mycosis fungoides and T-zone lymphoma including AIL-type) lymphomas and high-grade (large cell immunoblastic and polylobated and lymphoblastic) lymphomas (P less than 0.025). However, when survival of T-zone and AIL-like T-cell lymphoma was compared with survival of large cell immunoblastic and polylobated lymphomas no significant difference was detected. Age (less than 50 years) and stage I or II disease were associated with significantly better survival (P less than 0.005 and P less than 0.05).

Adolescent↗
PubMed1987

Immunohistological diagnosis of a case of composite lymphoma.

A case of composite lymphoma consisting of Hodgkin's disease and B cell lymphocytic lymphoma is described. A diagnosis of lymphocyte predominant Hodgkin's disease was made initially by histology. The presence of a composite lymphoma was only appreciated once immunohistochemistry was available. The findings illustrate the importance of the use of immunological markers for the accurate diagnosis of lymphoma.

Aged↗