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Biomedical subjects

B Fitzpatrick

Publications and source records attributed to B Fitzpatrick.

At least 19 recordsLinked to original sources

Desmopressin: therapeutic limitations in children and adults with inherited coagulation disorders.

Desmopressin (DDAVP), a synthetic analogue of vasopressin has been successfully used in the treatment of type I von Willebrand's disease (VWD), mild factor VIII (FVIII) deficiency and intrinsic platelet function defects (PFDs) for almost three decades. However, there is limited published data documenting its efficacy and the reliability of circulating plasma FVIII:C as a surrogate marker of response to therapy in VWD. We report the haemostatic response to DDAVP in 133 consecutive patients (91 type I VWD, 20 mild FVIII deficiency and 22 PFDs). Minimal therapeutic response to DDAVP (0.3 microg/kg) was defined by normalization 30 min post- infusion of bleeding time for PFDs, factor VIII:C (FVIII:C) for mild haemophilia A, and von Willebrand factor antigen (VWF:Ag), von Willebrand factor functional activity (VWF:Ac) and FVIII:C for VWD. Nine out of 91 (10%) VWD patients failed to achieve minimal therapeutic response to DDAVP; plasma FVIII:C levels were an unreliable surrogate marker of DDAVP response as 6 out of 9 (67%) of these patients had normal post-infusion FVIII:C levels. Five out of the 20 (25%) patients with mild FVIII deficiency and 5 out of 22 (23%) patients with PFDs failed to achieve a minimal therapeutic response to DDAVP. DDAVP is an effective therapy in the majority of patients with type I VWD, PFDs and mild FVIII deficiency. The significant failure rate associated with this therapy supports the recent recommendations that response should be assessed in all patients at the time of diagnosis. FVIII:C is an unreliable guide of response to DDAVP in patients with VWD and therefore VWF:Ag and VWF:Ac should also be assessed. Failure to demonstrate the response of VWF:Ag, VWF:Ac and FVIII:C to DDAVP in patients with VWD is likely to increase the risk of haemorrhagic complications in patients with bleeding episodes or who are undergoing surgery.

ABO Blood-Group System↗

Estrogen treatment enhances hereditary renal tumor development in Eker rats.

Hormonal influences are known to affect the development of renal cell carcinoma in man and laboratory animal models. We tested the hypothesis that estrogen treatment or ovariectomy of rats modulates renal tumor development using tuberous sclerosis 2 (Tsc2) heterozygous mutant (Eker) rats in which a germline mutation predisposes the animals to renal cell tumor development. Two-month-old female wild-type and Eker rats were ovariectomized or sham-operated and treated with placebo or 5 mg 17beta-estradiol in s.c. pellets for 6 or 10 months. Rats were examined at 8 or 12 months of age, at which time the numbers of renal tumors and preneoplastic foci were quantitated and the severity of nephropathy was assessed. In contrast to what may have been expected, prolonged estrogen treatment enhanced the development of hereditary renal cell tumors, with a 2-fold greater number of preneoplastic and neoplastic renal lesions compared with untreated Eker rats. Ovariectomized Eker rats had 33% fewer renal lesions than the unmanipulated control group. No tumors or preneoplastic lesions were present in wild-type rats at either time point. Estrogen treatment increased the severity of nephropathy in both wild-type and Eker rats, whereas ovariectomy was protective against nephropathic changes. Although estrogen is not a rat renal carcinogen, it enhanced the development of hereditary renal cell tumors when administered to Eker rats. Eker rats heterozygous for a mutation in the Tsc2 locus provide a good model in which to study how genetic and hormonal factors contribute to the development of renal cell tumors and to understand the influence genetic susceptibility has on the development of renal cell carcinoma.

Animals↗

Trans-antral temporalis transfer for the repair of adult cleft palates.

Temporalis muscle transfer is a versatile technique frequently used for reconstructive procedures in the maxillofacial region. However the thickness of the pedicle may interfere with masticatory function when used anteriorly in the oral cavity. To repair full-length mid-palatal defects in fully dentate patients the flap can be passed through the maxillary sinus and combined with local repair of the soft palate, thus avoiding any occlusal trauma from the posterior teeth. The operation is a single stage procedure with low morbidity and few complications, and is a useful technique for repairing the large untreated clefts frequently encountered in developing countries. The procedure is used by members of the Australian and New Zealand Association of Oral and Maxillofacial Surgeons Bangladesh Project who have operated in Dhaka teaching hospitals on a regular basis since 1991.

Adult↗

Sex differences in myocardial infarction and coronary deaths in the Scottish MONICA population of Glasgow 1985 to 1991. Presentation, diagnosis, treatment, and 28-day case fatality of 3991 events in men and 1551 events in women.

BACKGROUND: Scottish MONICA used medical and medico-legal records and World Health Organization MONICA Project criteria to register coronary events in 25- to 64-year-old residents of the high-incidence area of north Glasgow from 1985 to 1991. METHODS AND RESULTS: Age-standardized data from 3991 episodes of nonfatal definite myocardial infarction and coronary deaths in men (mean age, 55.5 years) were compared with 1551 in women (57.0 years). Many results, such as the overall 28-day fatality rates of 49.8% in men and 48.5% in women, showed insignificant differences. However, 74.3% of deaths in men occurred out of hospital versus 67.8% in women (P = .0004). After admission to hospital, fatality rates in women were 14% higher (P = .07) and after admission to coronary care, 22% higher (P = .04). Women were more often widowed. Fewer had a history of previous myocardial infarction, but the prevalence of angina pectoris, of smoking, and of chest pain in the attack was the same as in men; more had shock, syncope, and breathlessness. More consulted a doctor before admission to hospital, which delayed their coming under care. More men had ECG Q-wave progression, and more women had smaller ECG changes. This, and marginally reduced chances of direct admission to coronary care, of thrombolysis, of aspirin, and of beta-blockers, did not explain women's excess hospital fatality. CONCLUSIONS: Acute coronary events appear to be recognized and treated fairly equally in men and women 25 to 64 years old in Glasgow, so differences are small but subtle. More men die suddenly out of hospital; the reason why more women die after arrival may be because the equivalent number of men have already died outside.

Acute Disease↗

Out-of-hospital cardiac arrest due to coronary heart disease: a comparison of survival before and after the introduction of defribrillators in ambulances.

OBJECTIVE: To assess the actual impact on coronary mortality of equipping ambulances with defibrillators. DESIGN: Retrospective analysis of routine medical and legal records of all those who had a cardiac arrest attributed to coronary heart disease occurring outside hospital in a defined population before and after the introduction of Heartstart. SETTING: City of Glasgow, North of the River Clyde, 1984 and 1990. PATIENTS: 296 and 267 men and women aged 25-64 inclusive in 1984 and 1990 respectively who had a cardiac arrest outside hospital which was attributed to coronary heart disease (International Classification of Diseases codes 410-414, ninth revision). RESULTS: The impact on coronary mortality in 1990 of equipping ambulances with defibrillators concurred with the earlier prediction of less than 1% of all coronary deaths. The circumstances of cardiac arrest were largely unchanged; most occurred outside hospital in the victim's home and the principal witnesses were members of the victim's family. A call for help before cardiac arrest was made in very few cases and cardiopulmonary resuscitation was attempted by laypersons in less than a third of the deaths they witnessed. There was a significant increase in the number of cardiopulmonary resuscitation attempts made by ambulance crews (16% v 32%, P < 0.01). Ambulance crews, however, still attended less than half of all cases (44% and 47%). CONCLUSION: The impact of equipping ambulances with defibrillators will remain small unless strategies are introduced that focus on improving the public's response to coronary emergencies by calling for help promptly and initiating cardiopulmonary resuscitation before the arrival of the emergency services.

Adult↗

Use of computer graphic filters for the nuclear grading of hematoxylin and eosin-stained specimens from prostatic lesions.

An inexpensive workstation is being developed to assist pathologists in diagnosing routine hematoxylin and eosin-stained slides. A linear discriminant model was applied to karyometric features of prostate lesions, and a grade according to Mostofi was determined from the discriminant values. Twenty cases, five of hyperplasia and five each of carcinoma Mostofi grades I, II and III, for a total of 600 nuclei, were selected to train the model. Computer graphic filters were constructed from the discriminant values. Each segmented nucleus has a colored frame (the graphic filter) displayed around it. The color, determined from discriminant values and correlated with the grades, ranges from green for hyperplasia, yellow for low grade, orange for medium grade and red for high grade. An additional 20 cases, 5 of hyperplasia and 5 each of the Mostofi grades, for a total of 538 nuclei, were selected to test the graphic filter. Ninety-six percent of the hyperplasia nuclei were framed in green, 84% of low grade nuclei were framed in yellow, 90% of medium grade nuclei were framed in orange, and 89% of high grade nuclei were framed in red. These results indicate the potential of the color graphic filter to show the pathologist immediate and accurate visual information about the grade of a nucleus. This method may help with the difficult diagnosis of borderline lesions and may help in making the diagnosis from scanty biopsy material.

Cell Nucleus↗

Importance of different nuclear morphologic patterns in grading prostatic adenocarcinoma. An expanded model for computer graphic filters.

The aim of this work was to continue the development of an interactive workstation for the nuclear grading of prostatic lesions by including a large range of nuclear patterns. A previous model was based on four groups: hyperplasia, Mostofi grade 1, Mostofi grade 2 and Mostofi grade 3. Each group included the most common nuclear patterns of the lesions. One set used to test the model included cases showing patterns different from the typical ones of the model. Poor results were obtained for low and medium grades. A review of all the cases in our database led to the conclusion that different nuclear patterns can belong to the same "nuclear grade." Thus, in this work the model was expanded to include six groups: hyperplasia, two subgroups for Mostofi grade 1, two subgroups for Mostofi grade 2 and Mostofi grade 3. A set of 900 nuclei, 150 in each group, was selected to test the model. An additional 300 nuclei, 50 in each group, were used for a test set. The overall success rate for classifying the nuclei in the test set using the new model was 93% as compared to a rate of 71% obtained for the similar test set, described above, using the previous model. Moreover, correlating karyometric features with nuclear morphology indicated a role for nucleoli in nuclear grading. The good results obtained with large and heterogeneous sets of cases indicate that the procedures used to develop this model may be adapted for the development of models for the nuclear grading of other tumors.

Adenocarcinoma↗

Potential impact of emergency intervention on sudden deaths from coronary heart disease in Glasgow.

OBJECTIVE: To determine the potential impact of emergency intervention strategies to prevent deaths from coronary heart disease outside hospital. DESIGN: Analysis of routine medical and legal records of all persons dying of coronary heart disease in a defined population. SETTING: Glasgow City, north of the river Clyde, 1984. SUBJECTS: 420 people under 65 years for whom the underlying cause of death on the death certificate was coronary heart disease (ICD 410-414, 9th Revision). RESULTS: Of the 296 deaths outside hospital, 73% occurred at home. The deaths of 40% of those who died outside hospital were not witnessed and these people could not have received prompt cardiopulmonary resuscitation. Only 16% of the witnesses of a death attempted cardiopulmonary resuscitation before the arrival of a doctor or an ambulance crew. Over half (53%) of the cases in which cardiopulmonary resuscitation could have been attempted by a witness, but was not attempted, death occurred in the presence of the spouse or other close relative. Death occurred in the presence of a duty doctor or the ambulance crew in a maximum of 5% of deaths outside hospital. Ninety one per cent of people were dead before a call for help was made. CONCLUSION: Unless a greater proportion of patients receive cardiopulmonary resuscitation before emergency staff arrive at the scene the provision of emergency care staff with defibrillators is unlikely to have a significant impact on deaths outside hospital caused by coronary heart disease.

Adult↗

Bilateral traumatic internal carotid artery dissections: case report.

Bilateral internal carotid artery dissections after blunt cervicofacial trauma are rare, with 16 cases being previously published. Management is presumed to be an extension of the dominant therapy for unilateral dissection, that being anticoagulant therapy; however, bilateral stenoses engender questions of threat to total cerebral blood flow. We herein present a patient who suffered bilateral type B dissections and who then had progression of the process on anticoagulant therapy, resulting in an unusual carotid reconstruction.

Adult↗

Correlation between visual clues, objective architectural features, and interobserver agreement in prostate cancer.

Three pathologists evaluated a number of designated architectural features to assign grades to 41 cases of well- to moderately differentiated adenocarcinoma, and their opinions were compared. The consensus opinion was obtained and evaluated against objective measurements of glandular architecture that were obtained by morphometric techniques. The observers agreed on gland size, gland uniformity, and the number of glands per field in only 49%, 31%, and 39% of cases, respectively. There were significant differences in the Gleason grades assigned by observers. Paired matching of individual Gleason grades showed agreement among observers in 44% (18 of 41), 56% (23 of 41), and 75% (31 of 41) of cases, respectively. This level of interobserver disagreement occurred even though cases with predominant patterns were selected carefully and those with variable patterns were excluded. A direct relationship appears to exist between increasing Gleason grade and increasing glandular variability, and there is an inverse relationship between Gleason grade, gland lumen area, and the number of glandular nuclei, as assessed by a group of pathologists.

Humans↗

Bactericidal activity of ceftazidime in serum compared with that of ticarcillin combined with amikacin.

We compared the bactericidal activity of serum attained 1 and 6 h after the termination of infusions of either ceftazidime (2 g) or ticarcillin plus amikacin (5 g and 7.5 mg/kg, respectively) in 6 volunteers against a panel of the most common pathogens found in the blood of febrile granulocytopenic cancer patients. Ceftazidime consistently produced significantly higher serum bactericidal titers at both 1 and 6 h against all species of gram-negative bacilli. Its performance against Pseudomonas aeruginosa was especially impressive. The geometric mean titer against this organism was 1:41 at 1 h, contrasted with 1:12 for ticarcillin plus amikacin (P = 0.025). However, for Staphylococcus aureus, the geometric mean serum bactericidal titer of ceftazidime was 1:3.6 at 1 h and undetectable at 6 h. Ceftazidime shows promise as single-agent therapy for serious gram-negative bacillary infections. Whether this promise is fulfilled and whether the observed antistaphylococcal activity is adequate for empiric therapy in infected granulocytopenic patients need further investigation.

Adolescent↗

Comparison of the pharmacokinetics of ceftazidime and moxalactam and their microbiological correlates in volunteers.

We compared ceftazidime with moxalactam, a commonly utilized, currently available drug. The microbiological activities of ceftazidime and moxalactam were studied. In addition, single-dose pharmacokinetics and serum bactericidal activity 1 and 6 h after a 2.0-g, 30-min infusion of each drug were determined in a crossover study in human volunteers. In vitro, both drugs had MICs for 90% of the isolates of less than 1.0 microgram/ml against the common members of the family Enterobacteriaceae and of 8.0 micrograms/ml against Staphylococcus aureus. Against Pseudomonas aeruginosa ceftazidime was more active than moxalactam, the respective MICs for 90% of the isolates being 8 and 128 micrograms/ml. Mean half-lives were 1.75 (+/- 0.21) h for ceftazidime and 2.5 (+/- 0.38) h for moxalactam. The serum bactericidal titers for both compounds against Escherichia coli and Klebsiella pneumoniae were high. Titers against S. aureus 6 h after infusion were negative. The mean (geometric) serum bactericidal titer of ceftazidime against 31 strains of P. aeruginosa (1:44) was higher than that of moxalactam (1:3.4).

Adolescent↗

Current concepts in the surgical management of the atrophic mandible.

1. For the severely atrophic mandible surgery cannot be considered as a magical panacea. 2. Retention of teeth or tooth roots is important as we are unable to predict the degree of mandibular bone resorption relating to the innate vascular pattern. 3. More emphasis should be given to mylohyoid reduction as described in this paper. 4. A gain in stability by surgery should not be at the expense of retention. 5. Mucosal grafts are more satisfactory than skin grafts. 6. Bone graft augmentation in the future must be considered with great caution. 7. When removing denture hyperplasia which involves the sulcus, every effort must be made to preserve viable mucosa in order to reconstitute a resilient border seal.

Alveolectomy↗