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Biomedical subjects

P Furness

Publications and source records attributed to P Furness.

At least 19 recordsLinked to original sources

A randomized controlled trial of the diagnostic accuracy of internet-based telepathology compared with conventional microscopy.

AIMS: To compare the diagnostic accuracy of internet-based virtual microscopy with conventional light microscopy, in the context of renal biopsies assessed by participants in the UK National Renal Pathology External Quality Assessment (EQA) Scheme. METHODS AND RESULTS: 'Virtual slides' of current EQA cases were made available over the internet to participants in the scheme. The approach permitted what may reasonably be described as a randomized controlled trial of the diagnostic accuracy of this mode of telepathology, in the context of renal pathology. No significant difference in diagnostic accuracy could be detected between the diagnoses proffered on the basis of virtual slides and conventional slides; but using virtual slides took pathologists considerably longer. CONCLUSIONS: This result provides some encouragement for the implementation of such virtual slide-based telepathology systems. However, in failing to detect a difference, equivalence of diagnostic accuracy has not been proved; nor has the relevance of this result to other fields of histopathology been demonstrated. A decision to implement a diagnostic telepathology system requires consideration of numerous factors beyond diagnostic accuracy, including financial, legal, professional and ethical issues.

Diagnosis↗

Torsion of the testicular appendix: importance of associated acute inflammation.

BACKGROUND: Torsion of the testicular appendix is the commonest cause of acute scrotum in children. The histological picture of these cases is variable and many show a heavy acute inflammatory cell infiltrate, unlike the response to pure ischaemic necrosis in other organs. The clinical implications and consequences of this associated inflammation are not clear. METHODS: A retrospective review of all cases presenting with torsion of the testicular appendix between 1987 and 2005 was carried out. In all, 79 cases were reviewed and the degree of acute inflammatory cell infiltrate and other morphological parameters were assessed and compared with the patients' clinical, operative and postoperative findings. Stains for bacteria and fungi were examined. RESULTS: A positive correlation was found between the severity of acute inflammatory cell infiltrates and the longer duration of symptoms and presence of clinical evidence of torsion of the testicular appendages. No other association was detected between the pattern or degree of acute inflammatory cell infiltrate and any other clinicopathological variable that may indicate pyogenic infection. No bacteria or fungal elements were identified. Marked lymphatic dilation may be the only histological finding to indicate the presence of early torsion in cases of scrotal pain secondary to torsion of the appendix testis. CONCLUSION: Heavy acute inflammatory cell infiltrates in the torted testicular appendix can be regarded as marker of progression of this condition. Investigation for infection is therefore not necessary in such cases.

Acute Disease↗

Laparoscopic Palomo varicocelectomy in the adolescent is safe after previous ipsilateral inguinal surgery.

OBJECTIVE: To evaluate the outcome of laparoscopic Palomo varicocelectomy (LPV) in young boys who had undergone previous ipsilateral inguinal surgery (in whom potentially the arterial supply to the testicles may be compromised) in an attempt to assess its safety for the collateral vascular supply in such cases. PATIENTS AND METHODS: Over a 5-year period (1995-2000) 44 patients underwent LPV, where both the spermatic artery and vein were ligated high above the internal ring. Thirteen patients had undergone previous ipsilateral inguinal surgery, which included inguinal hernia repairs in five, orchidopexy in two, communicating hydrocele repair in three and previous varicocele repair in three. All patients were followed clinically at 3 months and 1 year after surgery. RESULTS: There were no complications related to laparoscopy or varicocele ligation. No patient developed ipsilateral testicular atrophy; moreover the testis size remained stable or was associated with compensatory growth in all patients. CONCLUSION: Previous inguinal surgery involving the ipsilateral testicle does not appear to affect the collateral blood circulation to the affected testis in boys who undergo LPV mass ligation of the internal spermatic vein and artery. LPV for varicocele is safe in boys who have undergone previous inguinal surgery, suggesting that an adequate collateral blood supply is present.

Adolescent↗

Design and initial evaluation of a low-cost 3-Tesla research system for combined optical and functional MR imaging with interventional capability.

A 3-Tesla research system has been developed for functional and interventional magnetic resonance imaging (MRI) procedures on animal models based on a low field niche spectrometer. Use of two stages of fourth harmonic frequency multiplication has allowed us to produce a high-frequency spectrometer with good frequency stability based on a low-frequency direct digital synthesizer. The system has been designed with the ability to introduce interventional tools such as biopsy needles, radiofrequency (RF) electrodes, and fiber optics for optical spectroscopy and thermal ablation as well as drug infusions to allow function to be studied in the presence of external challenges. Full MR-compatible physiologic support capability allows animals to be maintained in a stable condition over extended periods of study. Functional MR images have been acquired by using gradient echoes (TR/TE = 40/12 msec) from the rat whisker barrel cortex using electrical stimulation (5-V, 1.5-mA, 1-msec pulses at 5 Hz via two needle electrodes inserted into the rat whisker pad). Initial results using respiratory gas challenges of 100% N(2), 100% O(2), and 10% CO(2) have shown excellent agreement between single wavelength (633 nm) optical and functional MR time series with subsecond time resolution. The 1-mm copper electrodes for interventional radiofrequency ablation procedures were easily visualized in the superior colliculus by using gradient echo sequences. This novel, low-cost, high field system appears to be a useful research tool for functional and interventional studies of rat brain and allows concurrent optical spectroscopy. J. Magn. Reson. Imaging 2001;13:87-92.

Animals↗

The Banff 97 working classification of renal allograft pathology.

BACKGROUND: Standardization of renal allograft biopsy interpretation is necessary to guide therapy and to establish an objective end point for clinical trials. This manuscript describes a classification, Banff 97, developed by investigators using the Banff Schema and the Collaborative Clinical Trials in Transplantation (CCTT) modification for diagnosis of renal allograft pathology. METHODS: Banff 97 grew from an international consensus discussion begun at Banff and continued via the Internet. This schema developed from (a) analysis of data using the Banff classification, (b) publication of and experience with the CCTT modification, (c) international conferences, and (d) data from recent studies on impact of vasculitis on transplant outcome. RESULTS: Semiquantitative lesion scoring continues to focus on tubulitis and arteritis but includes a minimum threshold for interstitial inflammation. Banff 97 defines "types" of acute/active rejection. Type I is tubulointerstitial rejection without arteritis. Type II is vascular rejection with intimal arteritis, and type III is severe rejection with transmural arterial changes. Biopsies with only mild inflammation are graded as "borderline/suspicious for rejection." Chronic/sclerosing allograft changes are graded based on severity of tubular atrophy and interstitial fibrosis. Antibody-mediated rejection, hyperacute or accelerated acute in presentation, is also categorized, as are other significant allograft findings. CONCLUSIONS: The Banff 97 working classification refines earlier schemas and represents input from two classifications most widely used in clinical rejection trials and in clinical practice worldwide. Major changes include the following: rejection with vasculitis is separated from tubulointerstitial rejection; severe rejection requires transmural changes in arteries; "borderline" rejection can only be interpreted in a clinical context; antibody-mediated rejection is further defined, and lesion scoring focuses on most severely involved structures. Criteria for specimen adequacy have also been modified. Banff 97 represents a significant refinement of allograft assessment, developed via international consensus discussions.

Acute Disease↗

Isolated microscopic haematuria in the genitourinary clinic: the value of renal biopsy.

Isolated microscopic haematuria is a common finding in the genitourinary clinic. The conventional approach to investigation includes urological referral for cystourethroscopy if renal imaging is normal. However the diagnostic yield is very low; in particular urothelial malignancy at age < 40 years is rare. Glomerular disease is increasingly recognized as a common cause of microscopic haematuria. In this study 50 patients with persistent microscopic haematuria detected at a genitourinary clinic underwent renal biopsy. Twelve (24%) had an abnormal biopsy--IgA nephropathy 6 (12%), thin membrane nephropathy 3 (6%), other glomerulonephritis 3 (6%). In 7 others no abnormality was found but information was incomplete as electron microscopy was unavailable. It is important to establish these diagnoses since some patients will develop progressive renal disease. In this clinical setting renal biopsy will give diagnostic and prognostic information, protects from repeated urological investigation, and allows reassurance if renal histology is normal. Renal biopsy is recommended for patients age < 40 years with persistent microscopic haematuria. An algorithm for the investigation of microscopic haematuria is presented.

Adult↗

Larval foraging behaviour and competition in Drosophila melanogaster.

Populations of Drosophila melanogaster derived by bidirectional selection for high (HA) and low (LA) aggregated oviposition behaviour differ significantly in the duration of the larval period and adult size because of differences in the developmental profiles for feeding rate over successive phases of larval growth. Feeding rates of HA larvae are significantly lower than those of LA larvae during the flexible period of growth which precedes attainment of critical mass for pupation. Consequently the HA larvae have a slower mean rate of development. In the fixed postcritical period of development the feeding rates of HA larvae are significantly higher than those of LA larvae. This causes a greater postcritical growth increment and larger adult flies. HA and LA larvae respond adaptively by changing the expression of components of their foraging behaviour depending on whether they are in or out of food. LA larvae exhibit a more flexible pattern of response and are also more successful competitors when food resources are limiting.

Animals↗

Thromboxane receptor antagonism combined with thromboxane synthase inhibition. 5. Synthesis and evaluation of enantiomers of 8-[[(4-chlorophenyl)sulfonyl]amino]-4-(3-pyridinylalkyl)octanoic acid.

The enantiomers of 8-[[(4-chlorophenyl)sulfonyl]amino]-4-(3-pyridinylpropyl)octanoic acid (1) and its pyridinyl ether analog (2) were synthesized using the highly diastereoselective method of alkylation of acyloxazolidinone. These enantiomerically pure compounds were compared with the corresponding racemic compounds 1 and 2 for their in vitro activity. Compounds 1, 1R, and 1S and 2,2S, and 2R were equipotent as thromboxane receptor antagonists (TxRAs) and thromboxane synthase inhibitors (TxSIs) (IC50 = 2-30 nM). Upon oral administration to guinea pigs, the enantiomers inhibited the ex vivo U 46619-induced platelet aggregation with potency similar to that of the corresponding racemic compound. This indicates that the enantiomers have pharmacologic profile and bioavailability similar to that of the corresponding racemic compound.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Thromboxane receptor antagonism combined with thromboxane synthase inhibition. 2. Synthesis and biological activity of 8-(benzenesulfonamido)-7-(3-pyridinyl)octaonic acid and related compounds.

A series of arylsulfonamide alkanoic acids substituted with a 3-pyridinyl group along the aliphatic chain were synthesized and tested in vitro for their ability to antagonize thromboxane A2 (TxA2) receptors and inhibit thromboxane synthase. These compounds were found to potently inhibit the U 46619-induced aggregation of human platelets and to also inhibit TxA2 biosynthesis in a human microsomal platelet preparation. However, some members of the series, notably compound 21, were found to display agonist activity on the rabbit aorta TxA2 receptor. This unwanted agonist activity appeared to be related to the presence of a substituent beta to the arylsulfonamido group.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Thromboxane receptor antagonism combined with thromboxane synthase inhibition. 3. Pyridinylalkyl-substituted 8-[(arylsulfonyl)amino]octanoic acids.

A series of 8-[(arylsulfonyl)amino]octanoic acids substituted with a pyridinylalkyl group along the chain were synthesized and tested in vitro for their ability to both antagonize the binding of thromboxane A2 to its receptors and to inhibit the thromboxane synthase enzyme. This series of compounds were found to inhibit the U 46619-induced aggregation of human platelets and the U 46619-induced contraction of dog saphenous vein. The compounds also inhibited TxA2 biosynthesis in a human microsomal platelet preparation. The relative position of the pyridinylalkyl and arylsulfonamide groups had significant effects on the thromboxane receptor antagonist (TxRA) activity and thromboxane synthase inhibitor (TxSI) activity. Compounds with the pyridine ring at the 7- or 8-position of the octanoic acid side chain were weakly active as TxSI but behaved as potent TxRA at the platelet receptor for TxA2. However, these compounds were agonists at the vascular receptor. Substitution of the pyridinylalkyl group at the 2- or 3-position resulted in compounds with potent TxSI activity and weak TxRA activity. The activity profile of the compounds with the pyridinylalkyl substitution at the 4-, 5-, or 6-position was very desirable. Compound 22 with a pyridinylpropyl substituent at the 4-position was found to display extremely potent TxRA and TxSI properties.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗