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Biomedical subjects

M Fallon

Publications and source records attributed to M Fallon.

At least 19 recordsLinked to original sources
PubMed2006

Primary Whipple's disease of the brain: characterization of the clinical syndrome and molecular diagnosis.

BACKGROUND: Whipple's disease (WD) of the brain without evidence of systemic involvement is a rare illness that is difficult to recognize and potentially life-threatening. AIM: To elucidate the clinical features and diagnosis of primary WD of the brain. DESIGN: A single case study, with review of published data. METHODS: We linked the information about our patient with 956 citations to published WD material. We were able to identify 19 other patients with primary WD of the brain. RESULTS: Our patient was a 48-year-old woman who presented 2 years ago with generalized tonic/clonic seizures. WD of the brain was diagnosed after a life-threatening subacute deterioration leading to reduced consciousness and eye movement abnormalities. She had atrophy and gliosis of the right hippocampal formation, and nodular enhanc-ing lesions. She developed the syndrome of inappropriate ADH secretion, blepharospasm with a complete paralysis of vertical gaze, a severe amnesic syndrome, obstructive sleep apnoea, altered sleep physiology and CSF oligoclonal bands. Primary WD of the brain was diagnosed after PCR confirmed Tropheryma whipplei DNA in CSF and blood. She recovered after intravenous methylprednisolone, meropenem and cotrimoxazole. She has now survived for 24 months, lives independently and drives. Comparing our patient with the 19 others, two clinical syndromes were apparent, in both adults and children: (i) multifarious neurological symptoms and signs with a CT or MRI showing multiple nodular enhancing lesions; (ii) focal neurology secondary to solitary mass lesions. DISCUSSION: Primary WD of the brain may be diagnosed by recognition of these two clinical syndromes, and confirmed by the application of molecular biological techniques such as PCR.

Brain Diseases↗
PubMed2002

Tailoring an antibacterial peptide of human lysosomal cathepsin G to enhance its broad-spectrum action against antibiotic-resistant bacterial pathogens.

Neutrophils contain several cationic antimicrobial proteins or peptides (CAPs) that exert antibiotic-like action against bacteria. These host-derived antibiotics kill susceptible bacteria by oxygen-independent mechanisms. Considerable interest in their activity has been generated in recent years due not only to their likely important role in innate host defense against infection, but also their possible use as therapeutic agents in treating infections caused by antibiotic-resistant pathogens. We have studied the antibacterial properties of human lysosomal cathepsin G (cat G). This highly cationic serine protease contains at least three antibacterial regions that by themselves can exert antibacterial action against Gram-negative bacteria, such as Pseudomonas aeruginosa. Only one of these peptides, defined by residues 117-136 of full-length cat G, has bactericidal action against Gram-positive pathogens, such as Staphylococcus aureus. Due to the broad-spectrum antibacterial action of this peptide, we have sought to define the amino acids within its primary sequence required for this activity and have developed variants with improved activity. This review emphasizes the importance of both cationicity and hydrophobicity as necessary characteristics for the antibacterial action of CAPs. It also proposes the strategy that naturally occurring large human CAPs can be dissected to smaller CAPs and then modified to enhance their activity in vitro. This approach could prove beneficial to those interested in developing antimicrobial peptides as therapeutic agents.

Amino Acid Sequence↗
PubMed2001

Strategies to manage the adverse effects of oral morphine: an evidence-based report.

Successful pain management with opioids requires that adequate analgesia be achieved without excessive adverse effects. By these criteria, a substantial minority of patients treated with oral morphine (10% to 30%) do not have a successful outcome because of (1) excessive adverse effects, (2) inadequate analgesia, or (3) a combination of both excessive adverse effects along with inadequate analgesia. The management of excessive adverse effects remains a major clinical challenge. Multiple approaches have been described to address this problem. The clinical challenge of selecting the best option is enhanced by the lack of definitive, evidence-based comparative data. Indeed, this aspect of opioid therapeutics has become a focus of substantial controversy. This study presents evidence-based recommendations for clinical-practice formulated by an Expert Working Group of the European Association of Palliative Care (EAPC) Research NETWORK: These recommendations highlight the need for careful evaluation to distinguish between morphine adverse effects from comorbidity, dehydration, or drug interactions, and initial consideration of dose reduction (possibly by the addition of a co analgesic). If side effects persist, the clinician should consider options of symptomatic management of the adverse effect, opioid rotation, or switching route of systemic administration. The approaches are described and guidelines are provided to aid in selecting between therapeutic options.

Administration, Oral↗
PubMed2001

The effects of dihydropyridine and phenylalkylamine calcium antagonist classes on autonomic function in hypertension: the VAMPHYRE study.

The aim of the present study was to compare the effects of a long-acting dihydropyridine (amlodipine) and a nondihydropyridine (verapamil) on autonomic function in patients with mild to moderate hypertension. A total of 145 patients with a diastolic blood pressure (BP) between 95 and 110 mm Hg received 8 weeks of verapamil sustained release (240 mg) and amlodipine (5 mg) in a prospective randomized, double blind, cross-over study, both after 4 weeks of placebo. The 24-h autonomic balance was measured by analysis of 24-h heart rate variability and short-term autonomic control of BP by baroreflex sensitivity measurements. Plasma norepinephrine was sampled at rest. Blood pressure was equally reduced from 153/100 mm Hg to 139/91 mm Hg with verapamil and 138/91 mm Hg with amlodipine, P = .50/.59. The low- to high-frequency ratio (LF/HF), reflecting sympathovagal balance, was higher with amlodipine than with verapamil (4.66 v 4.10; P = .001). Baroreflex function was improved by both treatments; however, baroreflex sensitivity (BRS) was significantly higher with verapamil than with amlodipine (8.47 v 8.06 msec/mm Hg; P = .01). Plasma norepinephrine (NE) level was higher with amlodipine than with verapamil (1.59 v 1.32 nmol/L; P < .0001). Amlodipine induces a shift in sympathovagal balance, as measured by heart rate variability indices and plasma NE, toward sympathetic predominance compared with vagal predominance with verapamil. Short-term autonomic control of BP, as assessed by BRS, is more effectively improved by verapamil than by amlodipine. These contrasting effects on autonomic function suggest that the nondihydropyridine calcium antagonist verapamil may have additional beneficial effects beyond lowering BP compared with the dihydropyridine amlodipine.

Adult↗
PubMed2001

Contrasting effects of verapamil and amlodipine on cardiovascular stress responses in hypertension.

AIMS: To compare the effects of two long-acting calcium antagonists of different types on cardiovascular stress responses in hypertension. METHODS: One-hundred and forty-five patients with mild to moderate hypertension and a mean (+/- s.e.mean) age of 51 +/- 0.9 years received for 8 weeks the phenylalkylamine verapamil sustained release (240 mg) and the dihydropyridine amlodipine (5 mg) in a double-blind cross-over design, both after 4 weeks of placebo. Blood pressure, heart rate and plasma noradrenaline were monitored during 3 min of sustained isometric handgrip and 2 min of cold pressor. RESULTS: Blood pressure was equally reduced by both drugs. After 3 min handgrip, systolic blood pressure, heart rate and rate-pressure product were lower with verapamil compared with amlodipine. Verapamil attenuated the increases in systolic blood pressure (25 +/- 2 vs 30 +/- 2 mmHg, difference 4.6, 95% CI (1.0, 8.1), P < 0.01) and rate-pressure product (3.1 +/- 0.2 vs 3.6 +/- 0.3 x 10(3) mmHg x beats min(-1), difference 0.5, 95% CI (0.1, 0.9), P < 0.01) during handgrip compared with amlodipine. Similar results were observed during cold pressor. Plasma noradrenaline levels were lower with verapamil compared with amlodipine at rest and after both tests, but the increases in plasma noradrenaline were not significantly different. CONCLUSIONS: Verapamil is more effective in reducing blood pressure and rate-pressure product responses to stress compared with amlodipine. Although plasma noradrenaline is lower with verapamil at rest and after stress, the increase during stress is not different.

Adult↗
PubMed2001

Traceability of poultry and poultry products.

Traceability of animals and animal products is becoming an essential marketing requirement necessary to meet heightened consumer expectations, particularly with respect to food safety. Traceability is a fundamental part of the management and audit systems that have been developed to provide assurances to the consumer. Most poultry products are produced by large companies who control all facets of production to an extraordinary level. The primary breeding, commercial breeding and production stages of poultry production have had to develop comprehensive recording and traceability systems, for productivity rather than public health reasons. These systems are principally documentary trails on an individual flock basis. Each flock comprises a unit having the same or similar status. Individual identification of poultry is not generally practised commercially, except in elite breeding stock. Traceability systems are being expanded in the production, processing and distribution areas to accommodate consumer concerns regarding public health and other issues. The nature of the industry and the level of controls applied by the poultry sector can provide sound and sustainable guarantees to the consumer. Future development lies in the wider application of sophisticated computerised systems at primary and further processing levels, to ensure that traceability can be maintained.

Animal Husbandry↗
PubMed2000

Children's perception of speech in multitalker babble.

Children 5, 9, and 11 years of age and young adults attempted to identify the final word of sentences recorded by a female speaker. The sentences were presented in two levels of multitalker babble, and participants responded by selecting one of four pictures. In a low-noise condition, the signal-to-noise ratio (SNR) was adjusted for each age group to yield 85% correct performance. In a high-noise condition, the SNR was set 7 dB lower than the low-noise condition. Although children required more favorable SNRs than adults to achieve comparable performance in low noise, an equivalent decrease in SNR had comparable consequences for all age groups. Thus age-related differences on this task can be attributed primarily to sensory factors.

Adolescent↗
PubMed2000

The use of Scopoderm in palliative care.

The drug hyoscine has several indications for symptom control for patients with end-stage disease. The transdermal preparation, Scopoderm, is most widely used to control excess salivary secretions but it can also have a role in the management of terminal secretions and in the control of nausea.

Administration, Cutaneous↗
PubMed1999

Phosphorothioate oligodeoxynucleotides can selectively alter neuronal activity in the cochlea.

A growing body of evidence indicates that extracellular adenosine triphosphate (ATP) may have a major role in cochlear function. Antagonists of ionotropic ATP receptors (P2X2) have significant effects on cochlear potentials and distortion product otoacoustic emissions (DPOAEs). We tested whether antisense oligodeoxynucleotides (ODNs) would mimic the functional deficiencies induced by the ATP antagonists through binding to P2X2 ATP receptor mRNA and thereby reduce the number of ATP receptors expressed in the membrane of the cells. Both a phosphorothioate ODN (S-ODN) antisense and a phosphodiester ODN (P-ODN) antisense to the P2X2 sequence and random sense ODNs containing 21 nucleotides were administered chronically (7 days) to the guinea pig cochlea via the perilymph compartment. Sound evoked cochlear potentials (cochlear microphonic; summating potential; compound action potential of the auditory nerve, CAP; latency of the first negative peak in the CAP, N1 latency) and DPOAEs were monitored to assess the effects of the ODNs. Results indicate that the phosphorothioate derivatives of both the antisense and random sense ODNs suppressed the CAP and prolonged the N1 latency with no significant effect on the other parameters. The P-ODNs had no effect. Since both the antisense and random sense S-ODNs had the same effect, we conclude that the S-ODNs affected neuronal function in a manner that did not involve binding to the ATP receptor mRNA.

Adenosine Triphosphate↗
PubMed1999

Psychosocial recovery from adult kidney transplantation: a literature review.

Kidney transplantation is the preferred treatment for patients with end-stage chronic renal disease. There appears to be no recent and extensive review of the literature on psychosocial recovery from adult kidney transplantation. This comprehensive review considers literature on six aspects of patient recovery and rehabilitation: psychiatric sequelae, functional recovery, stress and coping, the psychological impact of failed kidney transplants, quality of life (QOL), and adherence with medications. We conclude that although studies have become both more ambitious and rigorous, there is a pressing need to move away from descriptive research toward carefully designed multidisciplinary psychological intervention studies with kidney transplant patients.

Activities of Daily Living↗
PubMed1999

Acetabular involvement in osteonecrosis of the femoral head.

When an arthroplasty is needed to treat osteonecrosis of the femoral head, the use of a component that replaces or resurfaces only the femoral head is often considered as an alternative to total hip replacement if the acetabulum appears radiographically normal. However, the long-term results of the use of endoprostheses have often been poor, secondary in part to progressive degeneration of the acetabular cartilage and to protrusio acetabuli. To help to explain these observations, we examined the acetabular cartilage in forty-one hips in which a primary total hip replacement had been performed because of osteonecrosis of the femoral head in association with a radiographically normal acetabulum. The cartilage in the superior, weight-bearing region of the acetabulum was grossly abnormal in forty of the forty-one hips and it was histologically abnormal in all thirty-three hips that were so evaluated. In all but one hip, gross degeneration of the cartilage was apparent, involving less than 20 percent of the acetabulum; the degeneration was graded as mild (superficial fibrillation and slight irregularity of the surface) in sixteen hips, moderate (moderate fibrillation, alteration in color and consistency, and thinning of cartilage without complete erosion to bone) in twenty hips, and severe (marked fibrillation, alteration in color and consistency, and marked thinning of cartilage with areas of complete erosion to bone) in four hips. These observations emphasize the fact that radiographs cannot demonstrate early degeneration of cartilage and that, by the time that an arthroplasty is needed, degenerative changes are already present in the acetabular cartilage of a high percentage of hips with osteonecrosis, even when radiographs of the acetabulum show no abnormalities. These findings should be kept in mind when a decision is being made regarding which type of arthroplasty should be done in a patient who has osteonecrosis of the femoral head and regarding when to do the procedure.

Acetabulum↗
PubMed1998

Conditioning the auditory system with continuous vs. interrupted noise of equal acoustic energy: is either exposure more protective?

The purpose of this study was to test the hypothesis that differences exist in the amount of protection provided by prior sound conditioning with continuous vs. interrupted, moderate-level noise. Differences were determined by monitoring the changes that occurred in cubic (2f1-f2) distortion product otoacoustic emission (DPOAE) amplitude growth functions subsequent to a traumatizing noise exposure (105 dB SPL, 1.0-2.0 kHz octave band noise presented 24 h per day for 3 days) in guinea pigs which had been conditioned with either continuous (89 dB SPL, 1.0-2.0 kHz octave band noise presented 24 h per day for 11 days) or interrupted noise (95 dB SPL, 1.0-2.0 kHz octave band noise presented on a 6-h 'on'/18-h 'off' schedule for 11 days) of equal acoustic energy. Results suggest that there are significant differences in the degree of protection provided by prior sound conditioning with the continuous and interrupted schedules of moderate-level noise used in this study. Specifically, the interrupted conditioning protocol afforded some degree of protection against the damaging effects of the traumatizing noise exposure, limited to frequencies above the noise exposure band. Conversely, there was a lack of any consistent and sizable protective effect found across the entire test frequency range for the continuous sound conditioning protocol.

Acoustic Stimulation↗
PubMed1998

Additional pharmacological evidence that endogenous ATP modulates cochlear mechanics.

In the cochlea, outer hair cells (OHCs) generate the active cochlear mechanics whereas the supporting cells, such as Deiters' cells and Hensen's cells, may play a role in both the active and passive cochlear mechanics. The presence of receptors for adenosine triphosphate (ATP) on OHCs, Deiters' cells and Hensen's cells indicates that endogenous ATP may have a role in cochlear mechanics. To explore this possibility, the effects of the ATP antagonist, pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS), were studied in guinea pig both in vitro on isolated OHCs, Deiters' cells, Hensen's cells and pillar cells using the whole-cell configuration of the patch-clamp technique, and in vivo on sound evoked cochlear potentials (cochlear microphonic, CM; summating potential, SP; compound action potential, CAP) and distortion product otoacoustic emissions (DPOAEs) using cochlear perilymphatic perfusion. Results show that PPADS (100 microM) reduced the inward current evoked by 5-10 microM ATP in OHCs, Deiters' cells, Hensen's cells and pillar cells. This effect of PPADS was slow in onset and was slowly reversed to a varying degree in the different cell types. In vivo application of PPADS in increasing concentrations reduced the sound evoked CAP, SP and increased N1 latency starting at about 0.33 mM (SP) and 1 mM (CAP and N1 latency). PPADS (0.33-1 mM) reversibly suppressed the initial value of the quadratic DPOAE and reversed the 'slow decline' in the quadratic DPOAE that occurs during continuous stimulation with moderate level primaries. These results, together with the similar effects of the ATP antagonist suramin reported previously (Skellett et al., 1997), may be evidence that endogenous ATP acting on cells in the organ of Corti alters cochlear mechanics.

Action Potentials↗
PubMed1998

Quality of life after renal transplantation.

End stage renal disease (ESRD) inevitably reduces the life-span of its victims. The treatment of choice for many patients is transplantation but this does not effect a cure. Its aim is to improve renal function and thus to enhance the patient's ability to enjoy as full a life as possible. However, surprisingly little research has been concerned with quality of life after transplantation. A small-scale, exploratory study employing a qualitative design was undertaken to compare stress and quality of life between five patients with ESRD awaiting transplantation and five patients who had received a graft within the previous 6 months. The desire to undergo transplantation was fuelled by patients' perceived need to 'get off dialysis' and to 'lead a normal life'. All patients had received abundant technical information about renal transplantation and pre-operative preparation but information concerning the negative effects of transplantation, including the side-effects of medication appeared lacking. It was not possible to determine whether this information had not been supplied or had been offered but forgotten or denied. For pre-transplantation patients the main sources of stress were the need to undergo dialysis, awaiting the summons to hospital and the social isolation imposed by having a chronic condition such as constant fatigue. Post-transplantation patients were remarkably free of anxiety considering the impositions placed upon them by frequent clinic attendance to monitor their condition. Quality of life improved dramatically after transplantation despite the persistence of renal symptoms and patients felt privileged to have been offered this treatment option.

Activities of Daily Living↗