GnRH and neuropeptide regulation of gonadotropin secretion from cultured human pituitary cells

Gonadotropin-releasing hormone (GnRH) and its superactive analogues are currently being used in the treatment of a number of endocrine disorders, such as endometriosis, precocious puberty, infertility and prostatic cancer. Selection of these analogues for clinical use have been previously based on their activities in animal models. This thesis has therefore investigated the binding characteristics of the human GnRH receptor, in comparison to those of the rat receptor, as well as the activities of a number of GnRH analogues for stimulating luteinising hormone (LH) and follicle stimulating hormone (FSH) secretion from cultured human pituitary cells. The establishment of a human pituitary bioassay system has further made possible the investigation of the direct regulatory roles of GnRH and other neuropeptides in man. To date, such studies in man have been performed in vivo and are thus complicated by the simultaneous interactions of numerous modulators

Quinsy tonsillectomy or interval tonsillectomy - a prospective randomised trial

Fifty-one patients with peritonsillar abscesses were randomised to undergo either quinsy tonsillectomy (aT) or interval tonsillectomy (IT), and the two groups were compared. The QT group lost fewer (10,3 v. 17,9) working days and less blood during the operation (158,6 ml v. 205,7 ml); haemostasis was easier and the operation was technically simpler in this group. There was no significant difference in length of hospital stay and neither group had intra- or postoperative complications. Only 64% of the IT group returned for tonsillectomy. In this study QT had distinct advantages over drainage and IT in the management of peritonsillar abscesses

Traceroute sampling makes random graphs appear to have power law degree distributions

The topology of the Internet has typically been measured by sampling traceroutes, which are roughly shortest paths from sources to destinations. The resulting measurements have been used to infer that the Internet's degree distribution is scale-free; however, many of these measurements have relied on sampling traceroutes from a small number of sources. It was recently argued that sampling in this way can introduce a fundamental bias in the degree distribution, for instance, causing random (Erdos-Renyi) graphs to appear to have power law degree distributions. We explain this phenomenon analytically using differential equations to model the growth of a breadth-first tree in a random graph G(n,p=c/n) of average degree c, and show that sampling from a single source gives an apparent power law degree distribution P(k) ~ 1/k for k < c

Myringoplasty - effects on hearing and contributing factors

Indications for myringoplasty are chronic otorrhoea and hearing impairment. Some authors have described poor postoperative hearing results and sensorineural hearing loss associated with the surgery, and question the indication for myringoplasty on an ear with normal hearing « 25 dB). This study of 211 Consecutive myringoplasties performed over 1 year details the 'take rate,' hearing gains and losses, and factors found to influence the above. The take rate of 78% is comparable with figures in the literature. The most significant factors influencing this are the grade of the surgeon and the size of the perforation. The average pre-operative air-bone gap was closed from 23,7 dB to 13,9 dB with a 4,5% incidence of postoperative sensorineural hearing loss. Postoperatively 77,9% of patients had an air-bone gap of less than 20 dB. We conclude that myringoplasty is a beneficial procedure, closing the tympanic membrane and improving the hearing

Geographical variation in certification rates of blindness and sight impairment in England, 2008-2009

To examine and interpret the variation in the incidence of blindness and sight impairment in England by PCT, as reported by the Certificate of Vision Impairment (CVI). Design: Analysis of national certification data. Setting: All Primary Care Trusts, England. Participants: 23 773 CVI certifications issued from 2008 to 2009. Main Outcome measures: Crude and Age standardised rates of CVI data for blindness and sight loss by PCT. Methods: The crude and age standardised CVI rates per 100 000 were calculated with Spearman's rank correlation used to assess whether there was any evidence of association between CVI rates with Index of Multiple Deprivation (IMD) and the Programme Spend for Vision. Results: There was high-level variation, almost 11-fold (coefficient of variation 38%) in standardised CVI blindness and sight impairment annual certification rates across PCTs. The mean rate was 43.7 and the SD 16.7. We found little evidence of an association between the rate of blindness and sight impairment with either the IMD or Programme Spend on Vision. Conclusions: The wide geographical variation we found raises questions about the quality of the data and whether there is genuine unmet need for prevention of sight loss. It is a concern for public health practitioners who will be interpreting these data locally and nationally as the CVI data will form the basis of the public health indicator ‘preventable sight loss’. Poor-quality data and inadequate interpretation will only create confusion if not addressed adequately from the outset. There is an urgent need to address the shortcomings of the current data collection system and to educate all public health practitioners

Colourings of cubic graphs inducing isomorphic monochromatic subgraphs

A $k$-bisection of a bridgeless cubic graph $G$ is a $2$-colouring of its vertex set such that the colour classes have the same cardinality and all connected components in the two subgraphs induced by the colour classes (monochromatic components in what follows) have order at most $k$. Ban and Linial conjectured that every bridgeless cubic graph admits a $2$-bisection except for the Petersen graph. A similar problem for the edge set of cubic graphs has been studied: Wormald conjectured that every cubic graph $G$ with $|E(G)| \equiv 0 \pmod 2$ has a $2$-edge colouring such that the two monochromatic subgraphs are isomorphic linear forests (i.e. a forest whose components are paths). Finally, Ando conjectured that every cubic graph admits a bisection such that the two induced monochromatic subgraphs are isomorphic. In this paper, we give a detailed insight into the conjectures of Ban-Linial and Wormald and provide evidence of a strong relation of both of them with Ando's conjecture. Furthermore, we also give computational and theoretical evidence in their support. As a result, we pose some open problems stronger than the above mentioned conjectures. Moreover, we prove Ban-Linial's conjecture for cubic cycle permutation graphs. As a by-product of studying $2$-edge colourings of cubic graphs having linear forests as monochromatic components, we also give a negative answer to a problem posed by Jackson and Wormald about certain decompositions of cubic graphs into linear forests.Comment: 33 pages; submitted for publicatio

Efficacy of endoscopic sinus surgery for paranasal sinus mucocele including modified endoscopic Lothrop procedure for frontal sinus mucocele

This study evaluated the efficacy of the modified endoscopic Lothrop procedure (MELP) for complicated frontal mucoceles and endoscopic marsupialization for other paranasal sinus mucoceles. It was a retrospective, consecutive case review of sinus mucoceles treated endoscopically by a single surgeon over a four-year period (1998-2002). There were 41 mucoceles in 28 patients, including 24 frontal, eight frontoethmoidal, three ethmoidal, five maxillary and one frontal mucocele. Twenty-one patients underwent the modified Lothrop procedure for frontal mucoceles, and seven underwent simple drainage and marsupialization for frontoethmoidal, ethmoidal and maxillary mucoceles. At median follow-up of 16 months, all patients had a patent mucocele opening. Patients treated by drainage and marsupialization did not have any complications or mucocele recurrence. All patients treated by the modified endoscopic Lothrop procedure had improvement in symptoms and signs. Four patients had minor complications including epistaxis and adhesions and five required further surgery. The average hospital in-patient stay was 2 ± 1.4 days. Endoscopic techniques, including MELP are effective in the short term for the management of complex and simple paranasal sinus mucoceles. MELP has a useful place in the management of mucoceles with a significant bony partition from an adjacent sinus or nasal cavity. It is also indicated when the mucocele is associated with loss of lateral support in the sinus with risk of medial-wall collapse of the orbital contents obstructing drainage.Jwu Jin Khong, Raman Malhotra, Dinesh Selva and Peter John Wormal

An algorithm for counting circuits: application to real-world and random graphs

We introduce an algorithm which estimates the number of circuits in a graph as a function of their length. This approach provides analytical results for the typical entropy of circuits in sparse random graphs. When applied to real-world networks, it allows to estimate exponentially large numbers of circuits in polynomial time. We illustrate the method by studying a graph of the Internet structure.Comment: 7 pages, 3 figures, minor corrections, accepted versio

Proximal genomic localization of STAT1 binding and regulated transcriptional activity

BACKGROUND: Signal transducer and activator of transcription (STAT) proteins are key regulators of gene expression in response to the interferon (IFN) family of anti-viral and anti-microbial cytokines. We have examined the genomic relationship between STAT1 binding and regulated transcription using multiple tiling microarray and chromatin immunoprecipitation microarray (ChIP-chip) experiments from public repositories. RESULTS: In response to IFN-γ, STAT1 bound proximally to regions of the genome that exhibit regulated transcriptional activity. This finding was consistent between different tiling microarray platforms, and between different measures of transcriptional activity, including differential binding of RNA polymerase II, and differential mRNA transcription. Re-analysis of tiling microarray data from a recent study of IFN-γ-induced STAT1 ChIP-chip and mRNA expression revealed that STAT1 binding is tightly associated with localized mRNA transcription in response to IFN-γ. Close relationships were also apparent between STAT1 binding, STAT2 binding, and mRNA transcription in response to IFN-α. Furthermore, we found that sites of STAT1 binding within the Encyclopedia of DNA Elements (ENCODE) region are precisely correlated with sites of either enhanced or diminished binding by the RNA polymerase II complex. CONCLUSION: Together, our results indicate that STAT1 binds proximally to regions of the genome that exhibit regulated transcriptional activity. This finding establishes a generalized basis for the positioning of STAT1 binding sites within the genome, and supports a role for STAT1 in the direct recruitment of the RNA polymerase II complex to the promoters of IFN-γ-responsive genes

6-Deoxyhexoses froml-Rhamnose in the Search for Inducers of the Rhamnose Operon: Synergy of Chemistry and Biotechnology

In the search for alternative non‐metabolizable inducers in the l ‐rhamnose promoter system, the synthesis of fifteen 6‐deoxyhexoses from l ‐rhamnose demonstrates the value of synergy between biotechnology and chemistry. The readily available 2,3‐acetonide of rhamnonolactone allows inversion of configuration at C4 and/or C5 of rhamnose to give 6‐deoxy‐d ‐allose, 6‐deoxy‐d ‐gulose and 6‐deoxy‐l ‐talose. Highly crystalline 3,5‐benzylidene rhamnonolactone gives easy access to l ‐quinovose (6‐deoxy‐l ‐glucose), l ‐olivose and rhamnose analogue with C2 azido, amino and acetamido substituents. Electrophilic fluorination of rhamnal gives a mixture of 2‐deoxy‐2‐fluoro‐l ‐rhamnose and 2‐deoxy‐2‐fluoro‐l ‐quinovose. Biotechnology provides access to 6‐deoxy‐l ‐altrose and 1‐deoxy‐l ‐fructose