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Biomedical subjects

M Hawthorne

Publications and source records attributed to M Hawthorne.

At least 19 recordsLinked to original sources
PubMed2001

Chemopreventive effects of soy protein and purified soy isoflavones on DMBA-induced mammary tumors in female Sprague-Dawley rats.

There are conflicting reports on the effect of soy and its components on mammary carcinogenesis in adult female rats, mainly because of different rodent models that are used in chemoprevention studies. The present study was undertaken to compare the tumor-preventative effects of soy protein isolate (SPI) and two of its isoflavones in a "standard" model that had been used for the identification of many chemopreventive agents. Six groups of female Sprague-Dawley rats were provided with modified cornstarch AIN-76A diets supplemented as follows: no additional agents (control), purified genistein (200 mg/kg diet), purified daidzein (200 mg/kg diet), genistein + daidzein (100 mg/kg diet each), SPI containing normal levels of isoflavones (SPI-n), or SPI depleted of isoflavones (SPI-d). Mammary carcinomas were induced by 7,12-dimethylbenz[a]anthracene (DMBA) introduced 1 wk after the animals began consuming the experimental diets. At the end of the study (120 days after DMBA treatment), no significant differences were found among the six groups with respect to tumor incidence or survival, nor was there a significant reduction in tumor multiplicity in the genistein or genistein + daidzein group. However, there was a 32% reduction in tumor multiplicity in the daidzein and SPI-n groups relative to the control group (P < 0.05). The most effective diet was SPI-d, which produced a 50% reduction in tumor multiplicity relative to the control (P < 0.01). The difference between the SPI-d group and the daidzein or SPI-n group was not significant. Median tumor latency was increased from 53 days in the control group to 68 days in the daidzein group and to 72 days in the SPI-d group, but these differences were not statistically significant. These results show that daidzein and SPI (with normal or low levels of isoflavones) are effective inhibitors of DMBA-induced mammary tumors in adult rats.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2001

Psychological reactions among family members of patients with implantable defibrillators.

OBJECTIVE: To describe psychological reactions among family members of patients receiving an implantable cardioverter/defibrillator (ICD) during the first 9 months after implantation. METHODS: Eighty-two family members (age 56+/-12 years, 74 percent female, 79 percent married, 88 percent Caucasian) of ICD patients completed questionnaires regarding their mood (Profile of Mood State), cognitive illness appraisals (Meaning of Illness Questionnaire) and coping strategies (Jalowiec Coping Scale) prior to ICD implantation, and as well as 1 and 9 months postoperatively. RESULTS: Total mood disturbance score (TMD), threat appraisal, and emotion- and problem-focused coping were highest prior to ICD implantation, and decreased during the first postoperative month showing stable values thereafter. There was no change in challenge appraisal. Multiple regression analysis found that the use of psychotropic drugs (anxiolytics, sedatives; Beta = .25), emotion-focused coping (Beta = .37), and challenge appraisal (Beta =-.21) at 1 month accounted for 26 percent of variance in TMD at 9 mon ths. CONCLUSION: A spouse's ICD implantation is a major stressful event for family members leading to a diminished mood state prior ICD implantation. Reduction in emotion-focused coping and the use of challenge appraisal may improve mood state in family members of ICD patients during early follow-up.

Adaptation, Psychological↗
PubMed2000

Prevention of N-methyl-N-nitrosourea-induced mammary carcinogenesis in rats by 1alpha-hydroxyvitamin D(5).

BACKGROUND: Although the active form of vitamin D, i.e., 1,25-dihydroxyvitamin D(3), is a potent cell-differentiating agent, its use in cancer prevention or therapy is precluded because it induces excessive blood calcium levels (hypercalcemia). However, less calcemic or noncalcemic synthetic analogues of vitamin D(3) are poorly effective against mammary carcinogenesis. We synthesized an analogue of vitamin D(5), 1alpha-hydroxy-24-ethylcholecalciferol (1alpha-hydroxyvitamin D(5)), which was less calcemic than 1,25-dihydroxyvitamin D(3) and prevented the development of precancerous lesions in mammary glands. Here, we evaluate its efficacy in an experimental rat mammary carcinogenesis model. METHODS: Sprague-Dawley rats were treated with 1alpha-hydroxyvitamin D(5) beginning 2 weeks before carcinogen treatment. Animals received an intravenous injection of N-methyl-N-nitrosourea at 80 days of age and continued to receive dietary 1alpha-hydroxyvitamin D(5) for an additional 105 days. Tumor incidence and multiplicity were determined, and plasma concentrations of calcium and phosphorus were measured. The efficacy of 1alpha-hydroxyvitamin D(5) at different stages of carcinogenesis was determined in mouse mammary gland organ culture. All statistical tests were two-sided. RESULTS: The tumor incidence was reduced from 80% (95% confidence interval [CI] = 51.9%-95.7%) in control rats to 53.3% (95% CI = 26.6%-78.8%) and 46.6% (95% CI = 21.3%-73.4%) in rats treated with 1alpha-hydroxyvitamin D(5) at 25 microg/kg diet and 50 microg/kg diet, respectively. The tumor multiplicity was reduced from 1.6 tumors per rat to 1.2 (95% CI for the difference = -0.45 to 1.25; P=.34) and 0.8 (95% CI for the difference = 0.14-1.46; P =.02), respectively. There was no statistically significant increase in the plasma calcium or phosphorus concentration at either dose level. The vitamin D(5) analogue was effective during both the initiation and the promotion stages of mammary lesion formation in organ culture. CONCLUSION: Our findings indicate that 1alpha-hydroxyvitamin D(5) reduces the incidence of mammary carcinogenesis in vivo. This analogue appears to be a good candidate for further development as a chemopreventive agent.

Animals↗
PubMed2000

A retrospective analysis of high resolution computed tomography in the assessment of cochlear implant patients.

High resolution computed tomography (HRCT) of the temporal bone is performed routinely in the preoperative evaluation for cochlear implantation. The largest multicentre retrospective analysis of data was undertaken to compare the findings on HRCT with the surgical findings in an attempt to determine the accuracy of HRCT. Of the 1009 patients referred, 525 were scanned of whom 335 were implanted. As part of this study we were also able to identify both radiological and non-radiological reasons for rejection of patients for cochlear implantation. the commonest cause being adequate residual hearing. The accuracy of HRCT in predicting cochlear ossification was 94.6%, with a 100% specificity and a 71%, sensitivity. Meningitis was the leading cause of cochlear ossification (44%). We conclude from this extensive multicentre study of both adult and paediatric patients that HRCT is accurate in predicting cochlear abnormality. In post-meningitic patients magnetic resonance imaging (MRI) may be a useful additional investigation.

Adult↗
PubMed2000

Quinine induced coagulopathy--a near fatal experience.

A 67 year old man presented to his local dentist for restorative treatment. He stated he was fit and well and denied taking any medications. When he was given an inferior alveolar nerve block, excessive bleeding was noted at the injection site and the dentist advised the patient see an oral and maxillofacial surgeon. An appointment was made for the patient but he did not attend. Three days later, he presented with evidence of massive deep haemorrhage to the point of airway compromise. He underwent hospital admission, early intubation, intensive care for nine days and hospitalization for six weeks. The cause of his bleeding was a severe thrombocytopoaenia, induced by chronic ingestion of quinine. He was self-medicating with this to relieve muscular cramps. Despite this experience, the patient continued to deny that quinine was the cause of his problem and that he had failed in his obligations to advise the dentist of his drug history. Dentists need to be alert to the risk that patients may not reveal their true medical history. There are, however, obligations on the dentist to ensure the accuracy of information the patient gives and to ensure that patients whom they believe are at risk follow their advice. Teamwork and skillful airway management prevented this patient's demise.

Aged↗
PubMed2000

Medialization of electrode array in cochlear implantation.

In the last few years, the main thrust of research into cochlear implantation has centred around the development of advanced multi-channel implants. A new area of development is now concentrating on maximizing the potential of each individual electrode in order to improve the quality of hearing. This study involved the medialization of the cochlear implant electrode array using a silastic positioner in five patients. Two parameters were measured, namely current units needed to produce a stapedial reflex, and impedance levels between the electrode and modiolus. On insertion of the cochlear implant, readings were taken before the insertion of the positioner, immediately afterwards and at two months.

Adult↗
PubMed2000

Pilocarpine for radiation-induced xerostomia in head and neck cancer.

This article examines the use of pilocarpine hydrochloride for radiation-induced xerostomia in patients with head and neck cancer. Four randomized controlled trials involving 401 patients met the authors' predefined inclusion criteria and were critically appraised. Three studies used topical pilocarpine as a mouthwash. Outcome measurements were both quantitative and qualitative. The studies reported statistically significant differences in favour of pilocarpine-stimulated treatment groups. Subjective improvements in feelings of oral dryness, speaking and chewing were reported in all studies. However, sample sizes varied and in all cases sampling methods were poorly defined. The pilocarpine doses tested produced side effects, but those reported were easily tolerated. The persistent findings of symptomatic improvement following pilocarpine use merit consideration, but there is insufficient evidence from these studies alone to generalize results to the wider population.

Head and Neck Neoplasms↗
PubMed1999

Association of mood disturbance and arrhythmia events in patients after cardioverter defibrillator implantation.

BACKGROUND: Life stresses and negative emotions, such as anxiety and depression, are associated with adverse cardiac events, including arrhythmia. Patients undergoing implantation of an automatic internal cardioverter defibrillator provide a unique opportunity to characterize these relationships since all tachyarrhythmia episodes are recorded by the device. OBJECTIVES: The purpose of this study was to examine the association of emotional status after internal cardioverter defibrillator (ICD) implantation and subsequent arrhythmia events. METHODS: An analysis of data obtained in a prospective longitudinal study of responses to the ICD measured mood disturbance (Profile of Mood States; POMS) before implant and at 1, 3, 6, and 9 months postoperatively. Subjects included 144 men and 32 women with a mean age of 60 +/- 13 years and a mean left ventricular ejection fraction (LVEF) of 33 +/- 12%. Arrhythmia events were measured by self-report of shocks and by ICD device interrogation to obtain the number and type (defibrillation, cardioversion, and antitachycardia pacing) of therapies delivered by the ICD. For each time point, POMS scores of subjects who had arrhythmia events were compared with those who did not. For subjects who had ICD shocks, pre-event and post-event POMS scores were also compared. Multiple logistic regression was used at each time point to determine if clinical, demographic and psychological data could predict arrhythmia events. RESULTS: Patients with arrhythmia events had higher POMS scores throughout the 9 months of follow-up. Higher level of mood disturbance (specifically anxiety, fatigue, and confusion) at 1 and 3 months were independent predictors of subsequent arrhythmia events at 3 and 6 months after controlling for LVEF, the presence of coronary artery disease, pre-implant arrhythmia history, and the use of amiodarone and beta-blocking agents. There were no differences in POMS scores before and after ICD shocks, reinforcing the notion that negative emotions were a cause, rather than a consequence, of arrhythmia events. CONCLUSIONS: Mood disturbances, such as anxiety, may increase the risk for arrhythmia events after ICD insertion.

Adult↗
PubMed1999

Unusual cases of congenital cholesteatoma of the ear.

Congenital cholesteatoma may originate at various sites in the temporal bone. For example, in the petrous apex, the cerebellopontine angle, the middle ear cavity, the mastoid process or the external auditory canal. The least common site being the mastoid process. We present two cases of congenital cholesteatoma of the mastoid process, each presenting with different symptoms and at different ages. Both patients underwent surgical treatment, which confirmed the diagnosis and radiological findings.

Adolescent↗
PubMed1999

Chemical labyrinthectomy and cochlear implantation for Menière's disease--an effective treatment or a last resort?

The surgical management of Menière's disease presents a difficult and controversial problem and includes various procedures ranging from 'placebo operations' to vestibular nerve section. The situation is even more complex in the case where the only hearing ear is affected. We present a case of severe debilitating vertigo due to Menière's disease that was treated by chemical labyrinthectomy and cochlear implantation. This unique management strategy allowed restoration of useful hearing and relief of vertigo.

Audiometry, Pure-Tone↗
PubMed1999

A three-array cochlear implant: a new approach for the ossified cochlea.

The ossified cochlea, although rare, represents a challenge for cochlear implantation. While it is no longer considered an absolute contra-indication to implantation, insertion may be technically difficult and the results may be suboptimal. Techniques which have been employed are reviewed. The new Digisonic multi-array implant, which was designed specifically for use in the ossified cochlea is described, along with the technique used for its insertion. In the first patient to be implanted with this new implant, all electrodes lie within the cochlea and are functional. The new Digisonic multi-array implant may have advantages over other solutions for the ossified cochlea.

Adult↗
PubMed1999

The subjective effects of smoking on nasal symptoms.

One hundred and forty-four volunteers completed a validated questionnaire, to investigate the association between smoking, non-smoking and passive smoking status, and the degree of a range of 10 common nasal symptoms. Logistic regression showed that smokers were four times and passive smokers six times more likely to report hyposmia compared to non-smokers. No significant differences were found between the three groups for any of the other nine symptoms.

Adolescent↗
PubMed1999

Impact of clinical practice guidelines on clinicians' behaviour: tonsillectomy in children.

OBJECTIVE: This study was conducted to assess the extent to which developing and implementing clinical practice guidelines for listing children for tonsillectomy (with or without adenoidectomy) influenced the behaviour of participating ENT surgeons. METHOD: A before and after study in which the intervention (the development and dissemination of local practice guidelines) was introduced sequentially into different hospitals and surgical practice. The study was conducted in four ear, nose, and throat surgical services in the North of England, with 16 consultant ENT surgeons and their junior staff on 1190 children aged 0 to 14 years who were judged, prior to consultation with an ENT surgeon, to have been referred for throat-related problems for which tonsillectomy was one possible treatment option were included in the study. Decision reached by surgeons and proportion of decisions that complied with new guidelines. RESULTS: Of the clinical decisions to list children for tonsillectomy taken before introduction of locally agreed guidelines, 73% (486/660) conformed to the criteria in the subsequent guidelines, 15% (97/660) did not, and in 12% (77/660), it was impossible to judge. After the intervention, the corresponding figures were 73% (386/530), 14% (73/53), and 13% (71/530), respectively. When decisions were taken to break the guidelines, this was more often to list for tonsillectomy when it was not indicated--83% (141/170)--than to withhold tonsillectomy when it was indicated--17% (29/170). The aspects of guidelines that were breached in decisions to carry out tonsillectomy were: the age of the child was younger than the guidelines recommended--54% (75/141); there had been fever attacks of tonsillitis than the guidelines recommended--22% (32/141); and there were "significant" symptoms not included in the guidelines--20% (29/141). CONCLUSIONS: In spite of strong evidence to the contrary, local guidelines were formulated at a level that the majority of surgeons already attained. Guideline development and implementation, therefore, had very little impact on clinical practice. The process of local formulation of guidelines was not sufficient to achieve change toward evidence-based practice; clinical preference proved to be quite intractable. There is a need to enhance the ability of clinicians in the assessment and interpretation of research evidence. Previous work has emphasized the need to explore factors that influence clinical behaviour toward evidence-based practice. Our study suggests the need for more research into why clinicians continue to follow clinical preference even when invited to base agreed local clinical policies on evidence.

Adolescent↗
PubMed1997

Cancer chemopreventive potential of sulforamate, a novel analogue of sulforaphane that induces phase 2 drug-metabolizing enzymes.

Chemoprevention involves the use of natural or synthetic substances to reduce the risk of developing cancer. Two dietary components capable of mediating chemopreventive activity in animal models by modulation of drug-metabolizing enzymes are sulforaphane, an aliphatic isothiocyanate, and brassinin, an indole-based dithiocarbamate, both found in cruciferous vegetables. We currently report the synthesis and activity of a novel cancer chemopreventive agent, (+/-)-4-methylsulfinyl-1-(S-methyldithiocarbamyl)-butane (trivial name, sulforamate), an aliphatic analogue of brassinin with structural similarities to sulforaphane. This compound was shown to be a monofunctional inducer of NAD(P)H:quinone oxidoreductase [quinone reductase (QR)], a Phase II enzyme, in murine Hepa 1c1c7 cell culture and two mutants thereof. Induction potential was comparable to that observed with sulforaphane (concentration required to double the specific activity of QR, approximately 0.2 microM), but cytotoxicity was reduced by about 3-fold (IC50 approximately 30 microm). In addition, sulforaphane, as well as the analogue, increased glutathione levels about 2-fold in cultured Hepa 1c1c7 cells. Induction of QR was regulated at the transcriptional level. Using Northern blotting techniques, time- and dose-dependent induction of QR mRNA levels were demonstrated in Hepa 1c1c7 cell culture. To further investigate the mechanism of induction, HepG2 human hepatoma cells were transiently transfected with QR-chloramphenicol acetyltransferase plasmid constructs containing various portions of the 5'-region of the QR gene. Sulforaphane and the analogue significantly induced (P < 0.0001) CAT activity at a concentration of 12.5 microM by interaction with the antioxidant responsive element (5-14-fold induction) without interacting with the xenobiotic responsive element. Moreover, both compounds significantly induced mouse mammary QR and glutathione S-transferase activity (feeding of 3 mg/mouse intragastric for 4 days), whereas the elevation of hepatic enzyme activities was less pronounced. Both sulforaphane and the analogue were identified as potent inhibitors of preneoplastic lesion formation in carcinogen-treated mouse mammary glands in organ culture (84 and 78% inhibition at 1 microm, respectively). On the basis of these results, the sulforaphane analogue can be regarded as a readily available promising new cancer chemopreventive agent.

Animals↗
PubMed1995

Verbal auditory agnosia with focal EEG abnormality: an unusual case of a child presenting to an ENT surgeon with "deafness".

Verbal auditory agnosia implies the failure to recognize sounds in a patient who is nevertheless not deaf. We present a child referred to the ENT outpatients for suspected hearing loss investigation. At one point she had grommets inserted on the basis of a flat tympanogram but with no effect. All hearing tests, including electrocochleography and distraction tests, revealed normal hearing thresholds. At the age of three years and three months, and on direct questioning of the parents, we discovered that the child responded remarkably well to music. Paediatric neurologists made the diagnosis of verbal auditory agnosia. The condition is very similar to another acquired language disorder called Landau-Kleffner syndrome. It is unusual for such a case to present primarily to an ENT surgeon.

Agnosia↗
PubMed1995

Cancer chemopreventive activity of brassinin, a phytoalexin from cabbage.

Brassinin [3-(S-methyldithiocarbamoyl)aminomethyl indole], a phytoalexin first identified as a constituent of cabbage, was synthesized and evaluated for cancer chemopreventive activity. Dose-dependent inhibition of 7,12-dimethylbenz[a]anthracene (DMBA)-induced preneoplastic lesion formation was observed with mouse mammary glands in organ culture, as was dose-dependent inhibition of DMBA-induced mouse skin tumors that were promoted by treatment with 12-O-tetradecanoylphorbol-13-acetate. Cyclobrassinin is a biologically derived product of the oxidative cyclization of brassinin, and was as active as the parent compound in inhibiting the formation of preneoplastic mammary lesions in culture; however, 2-methylbrassinin was not significantly active in this process. Therefore, oxidative cyclization may be an effective metabolic activation step. As judged by these tumor inhibition studies in conjunction with potential to induce phase II enzymes in mice or cell culture, brassinin may be effective as a chemopreventive agent during both the initiation and promotion phases of carcinogenesis. This is the first report documenting the chemopreventive potential of structurally novel indole-based phytoalexins that are naturally occurring in cruciferous vegetables, and the synthetic route described herein has proven amenable for scale-up production. The bifunctional structural nature of brassinin, bearing both an indole nucleus and a dithiocarbamoyl-aminomethyl moiety, is notably similar to the individual structural elements of other known chemopreventive agents such as indole-3-carbinol or benzylisothiocyanate. The favorable biological activity demonstrated by the compound may originate from the presence of these two moieties.

9,10-Dimethyl-1,2-benzanthracene↗