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Biomedical subjects

C Irving

Publications and source records attributed to C Irving.

At least 19 recordsLinked to original sources

Asymptomatic oropharyngeal lipoma complicating intubation.

Oropharyngeal lipomas are rare tumours. We present the case of a young man with an asymptomatic lipoma almost completely occluding his supraglottic airway, found on magnetic resonance imaging (MRI) for a separate oral cavity lesion. Pre-operative anaesthetic assessment was undertaken because of the risk of airway obstruction at induction of general anaesthesia. We discuss the awake fibre-optic technique used for induction, as well as the treatment and follow-up of these tumours. This case highlights the need for formal anaesthetic assessment, in such cases, to avoid total airway obstruction at induction of general anaesthesia. It also emphasizes the extent of supraglottic obstruction that can be present without giving rise to any symptoms.

Adult↗

Determinants of carotid microembolization.

PURPOSE: Earlier studies have highlighted risk factors for perioperative stroke after carotid endarterectomy, such as female sex, preoperative symptoms, and cerebral infarction. In this study, we investigated the relationship between these factors and perioperative microembolization. METHODS: A total of 235 patients were entered in the study at two centers. Transcranial Doppler ultrasound scanning was possible in 190 patients (81%) and was performed for 1 hour preoperatively and continuously intraoperatively as a means of detecting microemboli and monitoring mean middle cerebral artery velocity. The findings of transcranial Doppler ultrasound scanning were related to perioperative risk factors by means of univariate analysis. RESULTS: Microemboli were detected in 28 (15%), 79 (42%), and 98 (52%) patients preoperatively, during carotid artery dissection, and after closure of the artery, respectively. Having 10 or more emboli after carotid artery closure was more common in women (P = .04) and in patients with symptomatic carotid artery disease (P = .04) and was demonstrated in three of the six patients who had a perioperative stroke. These three patients also had preoperative evidence of cerebral infarction and an intraoperative middle cerebral artery velocity less than 40 cm/s. CONCLUSION: In this study, perioperative microembolization was more common in women and patients with symptomatic carotid artery disease. These findings may explain the increased risk of carotid surgery in these patients.

Adult↗

Signalling by FGF8 from the isthmus patterns anterior hindbrain and establishes the anterior limit of Hox gene expression.

Current evidence suggests that the anterior segment of the vertebrate hindbrain, rhombomere 1, gives rise to the entire cerebellum. It is situated where two distinct developmental patterning mechanisms converge: graded signalling from an organising centre (the isthmus) located at the midbrain/hindbrain boundary confronts segmentation of the hindbrain. The unique developmental fate of rhombomere 1 is reflected by it being the only hindbrain segment in which no Hox genes are expressed. In this study we show that ectopic FGF8 protein, a candidate for the isthmic organising activity, is able to induce and repress gene expression within the hindbrain in a manner appropriate to rhombomere 1. Using a heterotopic, heterospecific grafting strategy we demonstrate that rhombomere 1 is able to express Hox genes but that both isthmic tissue and FGF8 inhibit their expression. Inhibition of FGF8 function in vivo shows that it is responsible for defining the anterior limit of Hox gene expression within the developing brain and thereby specifies the extent of the rl territory. Previous studies have suggested that a retinoid morphogen gradient determines the axial limit of expression of individual Hox genes within the hindbrain. We propose a model whereby activation by retinoids is antagonised by inhibition by FGF8 in the anterior hindbrain to set aside the territory from which the cerebellum will develop.

Animals↗

Regulation and function of FGF8 in patterning of midbrain and anterior hindbrain.

In this article, an adjunct to a platform presentation at the Winternational 2000 Symposium, we summarize the recent findings of this group concerning the regulation and functions of FGF8 expressed at the isthmus of the developing brain. We show that several different FGF8 isoforms, ectopically expressed in midbrain or posterior forebrain, are able to mimic the proliferative and patterning functions previously attributed to the isthmus in tissue grafting studies. Moreover, we also show that FGF8 protein is sufficient to induce an ectopic isthmic organiser (Fgf-8+, Gbx2+) in anterior midbrain. We also provide evidence that isthmic FGF8 patterns anterior hindbrain, repressing Hox-a2 expression and setting aside a territory of the brain that includes the cerebellar anlage. We show that these effects of FGF8 are likely to be mediated via FGFR1 and be modulated by the putative FGF antagonist, Sprouty2, identified using a differential display screen. Finally, we provide evidence that the onset of Fgf8 expression is regulated by En1 and that its expression at the isthmus is subsequently maintained by a specific and direct interaction between rhombomere 1 and midbrain.

Animals↗

Droperidol for acute migraine headache.

The use of intramuscular droperidol to treat acute migraine headache has not been previously reported in the emergency medicine literature. It is a promising therapy for migraine. The authors performed a pilot review of all patients receiving droperidol for migraine in our emergency department (ED) to evaluate its efficacy. We used a retrospective case series, in a suburban ED with an annual patient census of 48,000. All patients with a discharge diagnosis of migraine headache who were treated with i.m. droperidol during a consecutive 5-month period in our ED were identified. All patients received droperidol 2.5 mg intramuscular. As per ED protocol, their clinical progress was closely followed and documented at 30 minutes after drug administration (t30). Demographic and clinical variables were recorded on a standardized, closed-question, data collection instrument. The primary outcome measurement was relief of symptoms at t30 to the point that the patient felt well enough to go home without further ED intervention (symptomatic relief). Thirty-seven patients were treated (84% female), with an ED diagnosis of acute migraine with droperidol during the study period. The mean age was 36 +/- 12 years. Analgesics had been used within 24 hours before ED presentation by 62% of patients. At t30, 30 (81%) patients had symptomatic relief, 2 (5%) felt partial relief but required rescue medication, and 5 (14%) had no relief of symptoms. Drowsiness (14%) and mild akathisia (8%) were the only adverse reactions observed following drug administration. Droperidol 2.5 mg intramuscular may be a safe and effective therapy for the ED management of acute migraine headache. Randomized, controlled trials are warranted to further validate the findings of this preliminary study.

Acute Disease↗

Regeneration of isthmic tissue is the result of a specific and direct interaction between rhombomere 1 and midbrain.

The midbrain-hindbrain boundary, or isthmus, is the source of signals that are responsible for regional specification of both the midbrain and anterior hindbrain. Fibroblast growth factor 8 (Fgf8) is expressed specifically at the isthmus and there is now good evidence that it forms at least part of the patterning signal. In this study, we use Fgf8 as a marker for isthmic cells to examine how interactions between midbrain and hindbrain can regenerate isthmic tissue and, thereby, gain insight into the normal formation and/or maintenance of the isthmus. We show that Fgf8-expressing tissue with properties of the isthmic organiser is generated when midbrain and rhombomere 1 tissue are juxtaposed but not when midbrain contacts any other rhombomere. The use of chick/quail chimeras shows that the isthmic tissue is largely derived from rhombomere 1. In a few cases a small proportion of the Fgf8-positive cells were of midbrain origin but this appears to be the result of a local respecification to a hindbrain phenotype, a process mimicked by ectopic FGF8. Studies in vitro show that the induction of Fgf8 is the result of a direct planar interaction between the two tissues and involves a diffusible signal.

Animals↗

Progressive spatial restriction of Sek-1 and Krox-20 gene expression during hindbrain segmentation.

After segmentation of the vertebrate hindbrain, expression of the zinc-finger gene Krox-20 and the receptor tyrosine kinase gene Sek-1 is precisely restricted to rhombomeres (r) 3 and 5. This precise segmental expression is likely to reflect a critical requirement for these rhombomeres to acquire a distinct and homogeneous identity and raises the question as to how this relates to the intermingling and restriction of cell movement during segmentation. We have analysed Krox-20 and Sek-1 expression in the mouse and chick hindbrain at single-cell resolution using whole-mount in situ hybridisation and immunocytochemistry. We find that, in the mouse, the presumptive r3 and r5 expression domains each arise as narrow stripes that then broaden, suggestive of a recruitment of cells to an r3/r5 identity and/or a segmental regulation of cell proliferation. In addition, we find that expression of these genes initially occurs in fuzzy domains, and that these are progressively restricted to segmental domains, although occasional "violating" cells are observed even after segmentation. We propose that the establishment and maintenance of these segmental domains may involve both a dynamic regulation of r3/r5 identity and the restriction of cell movement across rhombomere boundaries.

Animals↗

Expression and regulation of Cek-8, a cell to cell signalling receptor in developing chick limb buds.

The Eph-related receptor tyrosine kinase gene, Cek-8, is expressed in mesenchyme at the tip of chick limb buds, with high levels of transcripts posteriorly and apically but fading out anteriorly. Expression of Cek-8 in distal mesenchyme is regulated by apical ridge- and FGF-polarising signals and retinoic acid, and is uniform across the anteroposterior axis in talpid3 mutants. These data indicate that Cek-8 expression responds to regulatory signals during limb patterning and suggest that this receptor tyrosine kinase may have a role in coordinating responses to signals in the progress zone of early buds. Later on in limb development, Cek-8 expression is associated with cell condensations that form tendons and their attachments to cartilage rudiments and then in developing feather buds.

Animals↗

Cell-cell interactions and segmentation in the developing vertebrate hindbrain.

During development of the vertebrate hindbrain, regulatory gene expression becomes precisely restricted to specific segments. Studies at the cellular and molecular levels suggest that establishment of this precise pattern of gene expression may involve a dynamic regulation of cell identity and a restriction of cell movement across rhombomere boundaries. Candidates for mediating such interactions are several members of the Eph-related receptor tyrosine kinase (RTK) family that have segmental expression in the hindbrain. Ligands for members of this RTK family are membrane-bound, and may therefore mediate cell contact-dependent signalling. We discuss the expression patterns of Eph-related receptors in the hindbrain and the potential roles that these may play in patterning.

Animals↗

Energy expenditure variations in soldiers performing military activities under cold and hot climate conditions.

This study assessed the energetic status of soldiers exposed to intense physical activities in cold and warm weather. Thirty subjects participated in a two-phase study group A (n = 18) in the winter phase and group B (n = 12) in the summer phase. Energy expenditure (EE) was measured by the doubly labeled water technique; after a single, oral dosing of 2H(2)18O, daily urine samples were collected for 12 successive days. Energy intake (EI) was assessed from detailed food records analyzed by computerized food charts. Energy balance was calculated as the difference between EI and EE for each subject. Mean (+/- SE) daily EE was 4,281 +/- 170 and 3,937 +/- 159 kcal/day for the winter and summer groups, respectively. Daily EI was 2,792 +/- 124 kcal/day in group A and almost identical in group B. A negative energy balance of 1,422 +/- 163 kcal/day and 924 +/- 232 kcal/day (not significant) was calculated for groups A and B, respectively. Energy expenditure is primarily determined by the level of activity rather than by climate conditions; EI is insufficient to offset the high energy requirements under these conditions.

Adult↗

Broad spectrum penicillin as an adequate therapy for acute cholangitis.

In a previous study of patients with acute cholecystitis, we demonstrated equal efficacy with a broad spectrum penicillin (piperacillin) and a penicillin plus amino-glycoside combination. Whether a single agent broad spectrum penicillin is adequate treatment for more severe infections, such as acute cholangitis, however, is still unclear. We, therefore, conducted a three center, prospective, randomized trial to determine whether or not a broad spectrum penicillin alone is adequate therapy for patients with acute cholangitis. During a 36 month period, 96 patients with sepsis and biliary obstruction were randomly assigned to receive either piperacillin (n = 49) or ampicillin plus tobramycin (n = 47). The two groups receiving antibiotics were similar with respect to all clinical and laboratory parameters. The incidence of blood cultures with positive results (20 versus 21 per cent) and underlying malignant lesions (51 versus 62 per cent) was also similar between the two groups. The percentage of patients with a clinical cure or significant improvement was the same in the two groups (69 versus 70 per cent). However, there was a significant difference in the cure rate between patients with benign and malignant biliary obstructions (83 versus 59 per cent, p less than 0.01). No significant differences were noted between the two antibiotic groups with respect to drug toxicity, but patients with malignant conditions were more prone to antibiotic related toxicities (2 versus 19 per cent, p less than 0.05). These data suggest that outcome of treatment in patients with acute cholangitis is similar with either a broad spectrum penicillin or a penicillin plus aminoglycoside combination and is dependent upon the nature of the biliary obstruction.

Acute Disease↗

The pathology of nonpalpable breast cancer.

A principal goal of mammographic screening is the early detection of breast cancer. We reviewed records of 125 women who were referred because of nonpalpable, suspicious abnormalities on mammogram, which subsequently proved to be cancer, requiring mammographic localization biopsy and subsequent surgery for therapy. We found that 72 (57.6%) had invasive tumors, 15 (12%) showed evidence of microinvasion and 38 (30.4%) were noninvasive. A total of 115 patients had lymphadenectomy as part of their definitive surgery. Nine (12.7%) of the patients with infiltrating tumors had between one and 10 malignant nodes on histologic section. None of the patients with noninvasive or microinvasive tumors were found to have involved nodes. The mammographic abnormalities which led to biopsy in our series were: calcifications in 74 (59.2%) patients, mass lesions in 39 (31.2%), mass lesions with calcifications in 11 (8.8%), and asymmetry in one (0.8%). Of the nine patients with nodal metastases, seven (77.8%) had a mass with or without calcifications as the indication for biopsy. Increasing tumor size was found to correlate with invasive tumors on histopathologic examination and the incidence of lymph node metastases. Thirty-seven (54.4%) of the patients with infiltrating tumors had a tumor size greater than 1 cm. Further, seven (77.8%) of the nine lymph node positive patients had tumors between 1 and 3 cm in size. Of note, however, is that two (22.2%) patients with microscopic tumors had involved nodes. The 4-year actuarial survival in patients with infiltrating tumors was 85.2 per cent, while that for patients with noninvasive or microinvasive tumors was 100 per cent (median follow-up of 20 months).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗