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Biomedical subjects

J McCann

Publications and source records attributed to J McCann.

At least 19 recordsLinked to original sources
PubMed2003

The RAD30 cancer susceptibility gene.

The human skin cancer-prone disease xeroderma pigmentosum variant (XPV) results from a mutation in RAD30, which encodes the novel lesion bypass DNA polymerase eta. XPV cells are characterized by delayed completion of DNA replication and increased mutagenesis following UV irradiation. In cell-free extracts of XPV lymphoblasts, functional DNA polymerase eta is required for the complete replication of a double-stranded plasmid containing either a single (6-4) photoproduct or a cyclobutane pyrimidine dime(CPD), the major mutagenic UV-induced lesion. In cultured XPV cells, replication arrest activates downstream signalling pathways, leading to hyperphosphorylation of the 34-kDa subunit of the trimeric single-stranded DNA-binding protein, RPA (replication protein A). Many of the RAD30 mutations identified in XPV cells result in truncation and inactivation of DNA polymerase eta. To examine whether polymorphisms in the RAD30 gene that result in altered polymerase eta function, rather than enzyme inactivation, might contribute to individual susceptibility to skin cancer, methods to screen for sequence changes in the RAD30 gene in human genomic DNAhave been developed.

Animals↗
PubMed2003

Long-term survey of laryngoplasty and ventriculocordectomy in an older, mixed-breed population of 200 horses. Part 1: Maintenance of surgical arytenoid abduction and complications of surgery.

REASONS FOR PERFORMING STUDY: Laryngoplasty (LP) is currently the most common surgical treatment for equine laryngeal paralysis, however, there have been no reports quantifying the degree of retention of arytenoid abduction following LP. Additionally, the complications of LP have been poorly documented. OBJECTIVES: To record the degree of arytenoid abduction retention following LP and to accurately document all complications of surgery. METHODS: A study (1986-1998) of 200 horses of mixed breed and workload, median age 6 years (prospective 136 cases and retrospective 64 cases) undergoing LP (using 2 stainless steel wires) and combined ventriculocordectomy was undertaken; 198 owners completed questionnaires, a median of 19 months following surgery. The degree of arytenoid abduction achieved was endoscopically, semi-quantitatively evaluated using a 5-grade system, at 1 day, 7 days, and 6 weeks after surgery. RESULTS: On the day following LP, 62% of horses had good (median grade 2) arytenoid abduction, 10% had excessive (grade 1), and 5% had minimal (grade 4) abduction (overall-median grade 2). Due to progressive loss of abduction, moderate (median grade 3, range 1-5) abduction was present overall at 1 and 6 weeks after LP. Further surgery was required to re-tighten prostheses in 10% of cases with excessive loss of abduction, or to loosen prostheses in 7% of horses which had continuing high levels of LP abduction and significant post operative dysphagia. LP wound problems (mainly seromas and suture abscesses) were reported to last < 2 weeks in 9% of cases, < 4 weeks in 4% and > 4 weeks in 4%. The (partially sutured) laryngotomy wounds discharged post operatively for < 2 weeks in 22% of cases, < 4 weeks in 7% and for > 4 weeks in 2%. Coughing occurred at some stage post operatively in 43% of cases and its presence correlated significantly with the degree of surgical arytenoid abduction. This coughing occurred during eating in 24% of cases and was not associated with eating (or dysphagia) in the other 19% of cases. Chronic (> 6 months duration) coughing occurred in 14% of cases, but appeared to be due to intercurrent pulmonary disease in half of these horses. CONCLUSIONS: Suturing the cricotracheal membrane allows most laryngotomy wounds to heal quickly. Laryngoplasty wound problems were of little long-term consequence when stainless steel wire prostheses were used. POTENTIAL RELEVANCE: A significant loss of LP abduction occurs in most horses in the 6 weeks following surgery and efforts should be made to find ways to prevent such loss. However, excessive LP abduction is associated with post operative dysphagia and coughing.

Animals↗
PubMed2003

Long-term survey of laryngoplasty and ventriculocordectomy in an older, mixed-breed population of 200 horses. Part 2: Owners' assessment of the value of surgery.

REASONS FOR PERFORMING STUDY: There is continuing debate on the clinical benefit of laryngoplasty (LP) in the treatment of equine laryngeal paralysis. In particular, there is little information available on the clinical value of this surgery in older horses, in non-Thoroughbreds or in sports or pleasure horses; nor on the relationship between the degree of LP abduction achieved and the clinical value of LP. OBJECTIVES: To evaluate the owner's assessment of the value of LP (and combined ventriculocordectomy) in an older, mixed breed and mixed workload population of horses and to also assess the relationship between the degree of LP abduction present and the clinical value of this surgery. METHODS: A study (1986-1998) of 200 horses of mixed breed and workload, median age 6 years (prospective 136 cases and retrospective 64 cases) undergoing LP and ventriculocordectomy was undertaken. The degree of laryngoplasty abduction achieved and maintained was semiquantitatively evaluated using a 5-grade system. RESULTS: A survey of 198 owners, a median of 19 months after LP surgery, showed that 91% of cases had returned to full work and 3% to reduced work, including 95% of horses with good (Grade 2) laryngoplasty abduction at 6 weeks after surgery, 91% with moderate (Grade 3) abduction, 88% of cases with minsimal (Grade 4) abduction and just 25% of cases with total loss of surgical abduction (Grade 5). Once back in work, 73% of cases were reported to make no abnormal exercise-related noises ('noises') at exercise, with reduced 'noises' reported in some of the 21% of horses that still made 'noises'. In the other 6% of cases, owners were unsure if 'noises' were present. The absence or presence of 'noises' once back at work correlated significantly with the degree of surgical arytenoid abduction present at 6 weeks after LP. Once back in work, 'noises' were less commonly detected in sports and pleasure horses (absent in 76% of cases) than in racehorses (absent in 60%) of cases. Exercise performance following surgery was reported to be markedly increased in 75% of cases, with 10% showing no difference in exercise performance, 3% showing worse performance, and owners unsure of any effect on exercise performance in 13% of cases. Improved work was reported in 70% of sports and pleasure horses and in 67% of racehorses. Overall, 86% of owners believed LP was worthwhile, 7% believed it was not worthwhile and 6% were unsure of its value. Surgery was reported to be of most benefit to sports horses (e.g. reported worthwhile for 100% of show jumpers) and of least benefit to National Hunt (long distance) racehorses where 71% of owners believed it to be worthwhile. CONCLUSIONS AND POTENTIAL RELEVANCE: Most horse-owners believe that LP and combined ventriculocordectomy are of clinical value, especially in sports and pleasure horses. Large scale physiological studies on clinical cases, pre- and post operatively, are required to examine more critically the value of such surgery.

Age Factors↗
PubMed2002

Cocaine/heroin induced rhabdomyolysis and ventricular fibrillation.

A case of cardiorespiratory arrest in a 28 year old man after cocaine and heroin ingestion is described. The arrest is attributed primarily to hyperkalaemia/rhabdomyolysis-a recognised consequence of each of these drugs. The administration of naloxone may have been contributory. He developed acute renal failure, disseminated intravascular coagulopathy with consequent lower limb compartment syndrome requiring fasciotomy. Ventricular fibrillation was identified at thoracotomy.

Acute Kidney Injury↗
PubMed2002

Clinical and endoscopic evidence of progression in 152 cases of equine recurrent laryngeal neuropathy (RLN).

Examination of the long-term histories and clinical findings was performed in 351 horses suffering from recurrent laryngeal neuropathy (RLN) to examine for possible evidence of progression of this disorder. Fifty-two out of 351 cases (15%) had evidence of progression of the degree of laryngeal dysfunction over a median period of 12 months (range 1.5-48 months) with the onset of progression occurring at median age 7 years. In 30 cases, there was both endoscopic (median deterioration of 3 endoscopic grades; range 1-5 grades) and clinical evidence, with 29 (97%) of these horses concurrently developing sudden-onset, abnormal exercise-related respiratory 'noises' and 13 (43%) concurrently reporting reduced exercise performance. In the remaining 22 horses there was solely clinical evidence of RLN progression, including the sudden onset of abnormal exercise-related respiratory sounds in 16 (73%) and the worsening of such sounds in 6 (23%), associated with reduced exercise performance in 13 (59%) of these 22 cases. Endoscopically, 13 (59%) of the latter 22 cases had marked (total or almost total) RLN that did not appear compatible with their previous exercise-performance histories. This evidence of progression of RLN may be of particular significance in disputes concerning horses that are apparently normal at pre-purchase examination but are later shown to have RLN and also in the surgical treatment of less severe cases of RLN.

Animals↗
PubMed2001

Predicted long-term mortality reduction associated with the second round of breast screening in East Anglia.

Randomized trials have demonstrated that mammographic screening can reduce breast cancer mortality. Our aim was to estimate the reduction in mortality expected from the East Anglian Breast Screening Programme. Breast screening achieves benefit by improving cancer prognosis (reducing tumour size, nodal involvement and possibly grade) through earlier diagnosis. We compared cancer prognosis between women invited for screening and those not yet invited in East Anglia, UK, in order to predict the mortality reduction achievable by screening, independently of any reduction due to changes in treatment and underlying disease. Participants (both invited and not-yet invited) were women eligible for invitation to first and second screens and diagnosed with invasive breast cancer in 1989-96. Death rates were predicted based on the observed distribution of tumour grade, size and node status amongst 950 cancers diagnosed following first invitation, up to and including at second screen (excluding those detected at first screening), and 451 cancers presenting symptomatically in women awaiting first invitation during the staggered introduction of screening, after adjustment for lead time amongst screen detected cases. For all ages, the ratio of predicted breast cancer mortality in the invited compared with the uninvited group was 0.85 (95% CI 0.78, 0.93). It was 0.93 (0.80, 1.08) for women aged 50-54 at diagnosis and 0.81 (0.72, 0.91) for those aged 55-64. We conclude that, by 2004, the second round of screening in East Anglia should reduce mortality by around 7% in women below age 55 at diagnosis, and by around 19% in those aged 55-64.

Age Factors↗
PubMed2001

Interval cancer peer review in East Anglia: implications for monitoring doctors as well as the NHS breast screening programme.

AIM: To devise a method for reviewing interval cancers that will both educate radiologists and facilitate improvement of breast screening practice. To evaluate different methods for case classification to find one that best serves this purpose. METHOD: The method of peer review and the means by which interval cancers are classified is described. The way in which cases are designated false-negative is an issue of acceptability for radiologists, and so three different methods are evaluated. Each is applied to the data set collected in this region over a 3-year period. RESULTS: For cases read by five readers, when a consensus method was used for classifying cases, the proportion of cases classified as false-negative was 14%. Using a method in which only one of the five readers had to classify a case as false-negative for it to be categorized as such, the proportion of false-negative cases rose to a maximum of 38%. The minimum proportion of cases that could be considered to be false-negative was 6% and was obtained when all five readers had to classify a case as false-negative for it to be so categorized. Consistent with its majority viewpoint, the consensus method gave results for proportions of total cases classified as false-negative which were similar to those given by methods in which cases are classified as false-negative if either three of five readers, or at least 60% of readers, classified it as such. CONCLUSION: For the peer review method to achieve its dual aims of educating radiologists and auditing performance, the participating radiologists must share ownership of the results and view the analysis as fair. The method used to classify interval cancers as false-negative will influence the number so classified. A consensus method has been found to give a result that is both fair and acceptable to our radiologist. Using this method 16% of all reviewed cases were classified as false-negative and 60% as true interval cancers. Britton, P. D. (2001). Clinical Radiology56, 44-49.

Breast Neoplasms↗
PubMed2001

Comparison of neurologic outcome after deep hypothermic circulatory arrest with alpha-stat and pH-stat cardiopulmonary bypass in newborn pigs.

OBJECTIVE: Deep hypothermic circulatory arrest for neonatal heart surgery poses the risk of brain damage. Several studies suggest that pH-stat management during cardiopulmonary bypass improves neurologic outcome compared with alpha-stat management. This study compared neurologic outcome in a survival piglet model of deep hypothermic circulatory arrest between alpha-stat and pH-stat cardiopulmonary bypass. METHODS: Piglets were randomly assigned to alpha-stat (n = 7) or pH-stat (n = 7) cardiopulmonary bypass, cooled to 19 degrees C brain temperature, and subjected to 90 minutes of deep hypothermic circulatory arrest. After bypass rewarming/reperfusion, they survived 2 days. Neurologic outcome was assessed by neurologic performance (0-95, 0 = no deficit and 95 = brain death) and functional disability scores, as well as histopathology. Arterial pressure, blood gas, glucose, and brain temperature were recorded before, during, and after bypass. RESULTS: All physiologic data during cardiopulmonary bypass were similar between groups (pH-stat vs alpha-stat) except arterial pH (7.06 +/- 0.03 vs 7.43 +/- 0.09, P <.001) and arterial PCO (2) (98 +/- 8 vs 36 +/- 8 mm Hg, P <.001). No differences existed in duration of cardiopulmonary bypass or time to extubation. Performance was better in pH-stat versus alpha-stat management at 24 hours (2 +/- 3 vs 29 +/- 17, P = 0.004) and 48 hours (1 +/- 2 vs 8 +/- 9, P =.1). Also, functional disability was less severe with pH-stat management at 24 hours (P =.002) and 48 hours (P =.053). Neuronal cell damage was less severe with pH-stat versus alpha-stat in the neocortex (4% +/- 2% vs 15% +/- 7%, P <.001) and hippocampal CA1 region (11% +/- 5% vs 33% +/- 25%, P =.04), but not in the hippocampal CA3 region (3% +/- 5% vs 16% +/- 23%, P =.18) or dentate gyrus (1% +/- 1% vs 3% +/- 6%, P =.63). CONCLUSIONS: pH-stat cardiopulmonary bypass management improves neurologic outcome with deep hypothermic circulatory arrest compared with alpha-stat bypass. The mechanism of protection is not related to hemodynamics, hematocrit, glucose, or brain temperature.

Animals↗
PubMed2001

Mammographic parenchymal patterns and breast cancer natural history--a case-control study.

The relationship between tumour size, malignancy grade and dense mammographic parenchymal patterns was evaluated by using a nested case-control design with 875 breast cancer cases and 2 601 matched controls. Wolfe's classification was used to assess mammographic parenchymal patterns. The dense P2/DY mammographic parenchymal patterns were significantly associated with invasive ductal grade 3 carcinoma (OR = 2.03; 95%, CI 1.13-3.62, p = 0.016). Stratified by tumour size, we found that the odds ratio for grade 3 invasive ductal NOS breast cancer measuring 15-19 mm associated with P2/DY mammographic parenchymal patterns was 3.46 (95% CI 1.12-10.68). For tumours larger than 30 mm, the odds ratio was 10.09 (95% CI 1.27-79.93). The highest risk of grade 3 cancers being in tumours measuring 30 mm + may be due to dedifferentiation of missed cancers, but there is some excess even in the < 20 mm tumours, suggesting an increased risk in association with dense mammographic patterns of some aggressive cancers which are grade 3 at inception. Our results are consistent with the model that breast cancer is a progressive disease, whose development can be arrested by screening, and that the point at which individual tumour progression is stopped is crucial for prognosis not simply in terms of stage of disease, but also of histological grade.

Breast↗
PubMed2001

Desflurane confers neurologic protection for deep hypothermic circulatory arrest in newborn pigs.

BACKGROUND: Cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA), as used for infant heart surgery, carry a risk of ischemic neurologic injury. Volatile anesthetics have neuroprotective properties against both global and focal ischemia at normothermia. The authors examined the hemodynamic and neuroprotective effects of desflurane in a piglet CPB-DHCA model. METHODS: Twenty piglets aged 5-10 days received a desflurane- (6-9% expired) or fentanyl-based anesthetic before and during CPB (before and after DHCA). DHCA lasted 90 min at 19 degrees C brain. Cardiovascular variables (heart rate, arterial pressure, blood gases, glucose, brain temperature) were monitored. On postoperative day 2, neurologic and histologic outcomes were determined. RESULTS: Cardiovascular variables before, during, and after CPB were physiologically similar between groups. The desflurane group had better neurologic performance (P = 0.023) and greater postoperative weight gain (P = 0.04) than the fentanyl group. In neocortex, the desflurane group had less tissue damage (P = 0.0015) and fewer dead neurons (P = 0.0015) than the fentanyl group. Hippocampal tissue damage was less in the desflurane group (P = 0.05), but overall, neuronal cell counts in the CA1 sector of the right hippocampus were similar to those in the fentanyl group. CONCLUSIONS: Desflurane-based anesthesia yields hemodynamics during CPB with DHCA that are similar to those with fentanyl-based anesthesia. However, desflurane-based anesthesia improves neurologic and histologic outcomes of CPB-DHCA in comparison with outcomes with fentanyl-based anesthesia.

Anesthetics, Inhalation↗
PubMed2001

Radiological peer review of interval cancers in the East Anglian breast screening programme: what are we missing? East Anglian Breast Screening Programme.

OBJECTIVE: To determine whether association between classification of interval cancers (false negative, minimal sign, true interval, occult) and tumour characteristics can indicate areas for improvement in effectiveness of screening. SETTING: East Anglian regional Breast: Screening Programme. METHOD: The consensus classification of interval cases, obtained through peer review, was compared with tumour characteristics: size; grade; and nodal status, and with radiological signs. A set of 923 cancers with known tumour characteristics, presenting in unscreened women, was available for comparison. RESULT: In total, 385 interval cases were analysed. Prognosis of interval cancers was at least as good as that of cancers in unscreened women, with fewer node positive cases. No significant relation was found between classification of cases and age of patients. True intervals tended to present later after a negative screen, although false negatives commonly presented earlier. Occult cancers were significantly smaller than false negatives. Analysis of histological type yielded little of relevance, and mammographic appearance was similar in all classifications. At diagnosis, cancers in the low risk group were more likely to be seen as spiculate masses, whereas high risk cases more often appeared as opacities. A higher proportion of interval cases had been assessed than in the normal screened population. CONCLUSION: Sensitivity may be improved by reducing false negative and minimal sign cases (21% of interval cancers in East Anglia). These will include tumours in all risk groups, and with all radiological features, thus no particular age group or radiological feature may be targeted for improvement. Misdiagnosis at assessment reduces sensitivity and therefore merits particular study.

Aged↗
PubMed2001

Laryngeal paralysis: a study of 375 cases in a mixed-breed population of horses.

Referred cases (n = 375) of laryngeal paralysis (1985-1998) from a mixed-breed equine population included 351 (94%) cases of recurrent laryngeal neuropathy (RLN) (idiopathic laryngeal hemiplegia) and 24 cases (6%) of laryngeal paralysis from causes other than RLN. Laryngeal movements were classified endoscopically into one of 6 grades, in contrast to the usual 4 grades. The RLN cases had a median grade 4 laryngeal paralysis, of which 96% were left-sided, 2% right-sided and 2% bilaterally affected. RLN cases included 204 (58%) Thoroughbred, 96 (27%) Thoroughbred-cross, 23 (7%) draught, 16 (5%) Warmbloods and 10 (3%) other breeds, including only 4 (1%) ponies. The median age of RLN cases at referral was 6 years (range 2-12) and their median height was 170.2 cm. The work of RLN horses included National Hunt racing (42%), flat racing (1%), hunting (19%), eventing (16%) and miscellaneous work (22%). Reported presenting signs in RLN-affected horses included abnormal exercise-related respiratory sounds in 90% and reduced exercise tolerance in only 64%. However, many horses were referred before their exercise tolerance could be fully assessed. Forty percent of the RLN cases had intercurrent disorders, including 10% with additional upper respiratory and 7% with lower respiratory tract diseases. The 24 nonidiopathic RLN cases included 12 with bilateral laryngeal paralysis, 11 (92%) of which were ponies. Bilateral laryngeal paralysis occurred with hepatic encephalopathy in 7 cases and following general anaesthesia in 2 cases. The 12 cases of acquired unilateral laryngeal paralysis included 7 caused by guttural pouch mycosis.

Animals↗