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Biomedical subjects

F Johnston

Publications and source records attributed to F Johnston.

At least 19 recordsLinked to original sources
PubMed2003

High and low pressure states associated with posterior sacral meningocele.

We describe the rare cases of a 44-year-old woman and a 28-year-old woman each presenting with a large posterior sacrococcygeal mass and alternating symptoms of high and low intracranial pressure. The first patient underwent excision of her large sacral meningocele and simple ligation of the neck, resulting in resolution of all her associated symptoms. The second patient suffered traumatic rupture of the meningocele; she underwent excision of the redundant sac and repair of the dural defect using a musculofascial flap, also resulting in resolution of her symptoms.

Adult↗
PubMed2001

Endothelium-derived hyperpolarizing factor : identification and mechanisms of action in human subcutaneous resistance arteries.

BACKGROUND: Both a vascular endothelial cytochrome P450 (CYP450) product of arachidonic acid metabolism and the potassium ion (K(+)) have been identified as endothelium-derived hyperpolarizing factors (EDHFs) in animal vascular tissues. We studied the relative importance of EDHF, nitric oxide (NO), and prostacyclin (PGI(2)) as vasodilators in human subcutaneous arteries. We also examined the mechanisms underlying the vasodilator action of EDHF to elucidate its identity. METHODS AND RESULTS: Subcutaneous resistance arteries were obtained from 41 healthy volunteers. The contribution of EDHF to the vasodilation induced by acetylcholine was assessed by inhibiting production of NO, PGI(2), and membrane hyperpolarization. The mechanisms underlying the relaxation evoked by K(+) and EDHF were elucidated. EDHF was found to account for approximately 80% of acetylcholine-mediated vasorelaxation. Its action was insensitive to the combination of barium and ouabain, whereas barium and ouabain reversed K(+)-mediated vasorelaxation. EDHF-mediated vasorelaxation, however, was sensitive to the phospholipase A(2) inhibitor oleyloxyethyl phosphorylcholine and the CYP450 inhibitor ketoconazole. CONCLUSIONS: EDHF is the major contributor to endothelium-dependent vasorelaxation in human subcutaneous resistance arteries. A product of phospholipase A(2)/CYP450-dependent metabolism of arachidonic acid and not K(+) is the likely identity of EDHF in human subcutaneous resistance arteries.

Acetylcholine↗
PubMed2001

Signalling mechanisms underlying the myogenic response in human subcutaneous resistance arteries.

OBJECTIVE: In this study we have examined for the first time the signal transduction mechanisms involved in the generation of pressure-dependent myogenic tone in human small resistance arteries from the subcutaneous vascular bed. METHODS: Myogenic responses and the subcellular mechanisms involved in the generation of this response were studied on a pressure myograph. RESULTS AND CONCLUSION: Human subcutaneous resistance arteries constricted 14.1+/-1.1% in response to an increases in intraluminal pressure from 40 to 80 mmHg and a further 3.5+/-1.7% in response to the 80-120-mmHg pressure step. Ca(2+) depletion or nifedipine abolished this response, whereas BAY K 8644 increased this response to 20.6+/-2.1% (P<0.05, response vs. control). The phospholipase C inhibitor U-73122 reduced the myogenic response to 2.5+/-1.0% at 80 mmHg (P<0.01, response vs. control) and abolished it at 120 mmHg. Diacylglycerol lipase inhibition with RHC-80267 abolished all myogenic responses to pressure. The protein kinase C (PKC) activator phorbol 12,13-dibutyrate increased the maximal myogenic response to 20.9+/-1.8% (P<0.05, response vs. control), whereas the PKC inhibitor calphostin C abolished myogenic responses. These data show that the generation of pressure-dependent myogenic tone in human subcutaneous arteries is dependent on Ca(2+) influx via voltage operated Ca(2+) channels (VOCCs) and a concomitant requirement for the activation of phospholipase C (PLC), diacylglycerol, and PKC.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed2001

Effect of neutral endopeptidase inhibition on the actions of adrenomedullin and endothelin-1 in resistance arteries from patients with chronic heart failure.

Adrenomedullin and endothelin are novel peptides that are produced in the blood vessel wall and have contrasting biologic actions. Both may play a pathophysiological role in atherosclerosis and chronic heart failure. It has also been suggested that both peptides may be metabolized by neutral endopeptidase and that pharmacological manipulation of this enzyme may be of therapeutic interest. We investigated the effect of thiorphan, a neutral endopeptidase inhibitor, on the vasodilator response to adrenomedullin and the vasoconstrictor response to endothelin in small resistance arteries taken from patients with heart failure caused by coronary heart disease. Small resistance arteries were dissected from gluteal biopsy samples and studied with wire myography. Thiorphan did not affect the vasodilator response to adrenomedullin in arteries preconstricted with norepinephrine. Maximal responses were 66% (SD 11%) and 72% (8%) in the absence and presence of thiorphan, respectively (n=8). The vasoconstrictor response to endothelin was also unaffected. The maximum vasoconstrictor responses in the absence and presence of thiorphan were 152% (11%) and 132% (12%), respectively (n=8). The values of corresponding -log concentrations of agonist required to effect a 50% response (pD(2)) were 8.52 (0.11) and 8.64 (0.15), respectively. We showed that the inhibition of neutral endopeptidase does not augment the vasodilator and vasoconstrictor activities of adrenomedullin and endothelin, respectively, in small resistance arteries from patients with chronic heart failure. This suggests that neutral endopeptidase inhibition, as a therapeutic strategy, will enhance neither the potentially desirable vascular actions of adrenomedullin nor the potentially unfavorable vascular effects of endothelin-1 in human cardiovascular disease states.

Adrenomedullin↗
PubMed2001

Effect of adrenomedullin on the production of endothelin-1 and on its vasoconstrictor action in resistance arteries: evidence for a receptor-specific functional interaction in patients with heart failure.

Endothelin-1 (ET-1) and adrenomedullin (ADM) are both produced in the arterial wall, but have opposing biological actions. Evidence from experimental animals suggests a functional interaction between ET-1 and ADM. We have tested this in humans. Small resistance arteries were obtained from gluteal biopsies taken from patients with chronic heart failure (CHF) due to coronary heart disease (CHD), or with CHD and preserved ventricular function. The contractile responses to big ET-1 and to ET-1 in both sets of vessels were studied in the absence (control) and presence of ADM at 20 pmol/l (low ADM) or 200 pmol/l (high ADM), using wire myography. ADM did not affect the conversion of big ET-1 into ET-1 in vessels from patients with either CHD or CHF. Low ADM did not alter the contractile response to ET-1 in vessels from patients with CHF. Low ADM was not tested in vessels from patients with CHD, but high ADM did not affect this response in arteries from these patients. High ADM did, however, significantly reduce the vasoconstrictor effect of ET-1 in vessels from patients with CHF. The maximum response, as a percentage of the response to high potassium, was 199% (S.E.M. 25%) in the control experiments (n=14), 205% (27%) in the low-ADM (n=7) studies and 150% (17%) in the high-ADM (n=6) experiments (P<0.001). Furthermore, the Hill coefficient increased from 0.57+/-0.05 in the absence of ADM to 1.16+/-0.15 in the high-ADM experiments, indicating that ADM at 200 pmol/l specifically antagonized one receptor type in vessels from patients with CHF. We conclude that there is a one-site receptor interaction between ADM and ET-1 that is specific for vessels from patients with CHF. This functional interaction between ADM and ET-1 in resistance arteries may be of pathophysiological importance in CHF.

Adrenomedullin↗
PubMed2001

Functional characterization of alpha1-adrenoceptor subtypes in human subcutaneous resistance arteries.

The functional characteristics of the alpha1-adrenoceptor subtypes in human resistance arteries are still not clear. We recently reported that the alpha1A-adrenoceptor predominantly mediates contraction to norepinephrine in human skeletal muscle resistance arteries. In this study we extended these investigations to human subcutaneous resistance arteries. Arterial segments were isolated from the inguinal subcutaneous fat and mounted on a small vessel wire myograph. Potencies of agonists and antagonists were examined. N-[5-(4,5-dihydro-1H-imidazol-2yl)-2-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl]methanesulphonamide (A-61603) was found to be 10- and 54-fold more potent than norepinephrine and phenylephrine, respectively. Brimonidine (UK 14304) evoked significantly smaller contractile responses than norepinephrine and phenylephrine, showing the presence of a small population of alpha2-adrenoceptors in these arteries, and this was confirmed by the studies with selective alpha1- and alpha2-adrenoceptor antagonists prazosin and (8aR,12aS,13aS)-5,8,8a,9,10,11,12,12a,13a-decahydro-3-methoxyl-12-(ethylsulphonyl)-6H-isoquino[2,1-g][1,6]-naphthyridine (RS 79948). Prazosin, 5-methyl-urapidil, and 2-[2,6-dimethoxyphenoxyethyl]aminomethyl)-1,4-benzodioxane (WB 4101) shifted the potency of norepinephrine concentration dependently giving pA2 values of 9.4, 8.9, and 10.1, respectively, showing the presence of the alpha1A-subtype in these arteries. Pretreatment with 1 and 10 microM chloroethylclonidine did not affect the potency of and maximum responses to norepinephrine, ruling out the presence of the alpha1B-subtype in these arteries. 8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione (BMY 7378, 10 and 100 nM) did not affect the potency of norepinephrine but a small shift was observed by 1 microM BMY 7378, giving a pK(B) value of 7.1, much less than that reported for the alpha1D-subtype. These results suggest the predominant involvement of alpha1A-adrenoceptor in the contractile responses to norepinephrine in these arteries. The physiological role of this subtype in the maintenance of peripheral arterial resistance is yet to be confirmed.

Adrenergic alpha-Agonists↗
PubMed1999

Delays in stroke referrals.

Assessment of acute stroke by hospital physicians will have to speed up if we are to expect referral to hospital and computed tomography (both previously targets of criticism) to improve.

Acute Disease↗
PubMed1999

Evaluating the use of penicillin to control outbreaks of acute poststreptococcal glomerulonephritis.

INTRODUCTION: Outbreaks of acute poststreptococcal glomerulonephritis (APSGN), occur every few years in remote Australian Aboriginal communities. Intervention with benzathine penicillin G (BPG) to all children is effective in reducing streptococcal carriage in a community, but its effectiveness in arresting outbreaks of APSGN has not been established. OBJECTIVE: To study nine recent community outbreaks of APSGN in Australia's Northern Territory and compare them with outbreaks reported in the literature to assess the impact of intervention with BPG. METHODS: Because randomized controlled trials have not been conducted for this purpose, we assessed data from published observational studies and relevant experiences in the Northern Territory (NT). Eight of the nine outbreaks in the NT were studied prospectively. An outbreak was defined as two or more clinical cases of APSGN occurring within 1 week in a single community. Three intervention methods were used: intramuscular BPG to all children ages 3 to 15 years; BPG only to children with skin lesions; and BPG only to child contacts of clinical cases. The attack rates, number of clinical cases before and after the interventions were documented and the coverage of children with penicillin were estimated. RESULTS: A review of the literature found very little evidence either for or against the effectiveness of intervention with BPG. In our study four communities used the first method of intervention. The community with the lowest uptake of penicillin continued to have cases in untreated children for 9 further weeks, two communities had no new cases from 3 weeks after the intervention and the fourth had a single further case after 4 weeks. The one community that used the second method had a high initial attack rate but no further cases from 1 week after the intervention. Three communities used the third method and in one community no intervention was attempted. CONCLUSION: Our observational study supports the use of BPG in the community to prevent new cases of APSGN. It suggests that targeted treatment of children with skin sores and household contacts of cases, rather than attempted treatment of all children in the community, could be an effective method of intervention.

Acute Disease↗
PubMed1999

Subaxial cervical synovial cyst presenting with myelopathy. Report of three cases.

Synovial cysts occur infrequently in the spinal canal and are most often associated with degenerative facet joints. Despite the prevalence of degenerative spinal disease, symptomatic synovial cysts are extremely uncommon. There have been only two previously reported cases of subaxial degenerative synovial cysts of the cervical spine in patients who presented with a clinical picture of spinal cord compression. The authors report three additional patients treated for degenerative cervical synovial cysts who presented with myelopathy. In all three patients the cyst was successfully excised and a good clinical outcome achieved.

Aged↗
PubMed1997

An outbreak of influenza B among workers on an oil rig.

An outbreak of influenza B occurred in December 1996 on an oil rig in Darwin Harbour. The outbreak affected 56% of the workers on the rig. An outbreak in December is outside the usual Australian influenza season of June to September, but is consistent with other tropical regions, where outbreaks can occur throughout the year. Influenza vaccination could prevent similar outbreaks in confined workplaces.

Disease Outbreaks↗
PubMed1997

Expressive pragmatic skills in pre-school children with and without Down's syndrome: parental perceptions.

Parental perceptions of the pragmatic skills of six pre-school children with Down's syndrome were compared to those of six children without cognitive impairment. Children were matched for language comprehension age on the Reynell Developmental Language Scale and parents were interviewed using the Pragmatics Profile of Early Communication Skills. Data from the parental interviews was analysed taking a qualitative approach, using the technique of content analysis. The results showed that the children with and without Down's syndrome had many similarities in reported behaviours and responses In addition, five out of the six children with Down's syndrome had some skills which were more advanced than their matched pairs. Possible reasons for these findings are discussed. The evidence suggests that children with Down's syndrome have a normal range of pragmatic skills and communicative intentions compared with children of similar levels of comprehension functioning at an early pre-school level.

Child, Preschool↗
PubMed1997

A community-based approach to the control of sexually transmitted diseases in the Northern Territory.

A program to control sexually transmitted diseases (STDs) was undertaken during a Men's Health Week in a remote Aboriginal community in Western Arnhem Land, Northern Territory. A total of 151 men aged 13 years and over who attended over a five-day period underwent a full physical examination, and first-void urine specimens were tested for the presence of leukocytes, chlamydia (by enzyme immunoassay antigen detection) and gonorrhoea (by culture and antigen detection). Blood was taken for syphilis serology from all patients and for human immunodeficiency virus (HIV) from patients with a proven STD or at the patient's request. Consent for testing was obtained from all participants. Patients with a positive urinary leukocyte test or symptoms were offered urethral swab investigations and treated empirically according to a set protocol. Patients with STDs detected by subsequent laboratory investigations were followed up and treated. The overall prevalence of one or more of syphilis, gonorrhoea or chlamydia was 17.4 per cent. No men presented with genitourinary symptoms and none was HIV-infected. In this population, STDs were an important cause of morbidity, and a community-based approach was adopted to identify infected persons. The use of urine for the detection of gonorrhoea and chlamydia was highly acceptable. Although not used in this study, polymerase chain reaction and ligase chain reaction technology will facilitate similar activities in the future.

Adolescent↗
PubMed1995

Adenocarcinoma of Meckel's cave: case report.

A rare localization of adenocarcinoma in Meckel's cave is reported in a 58-year-old woman, who had a 5-month history of pain and altered sensation in the second division of the left trigeminal nerve. Removal of the lesion was achieved by a subtemporal route. Histology showed this to be an adenocarcinoma. The patient underwent investigations for a primary tumor; the investigations were all negative, and the patient was subsequently treated with a course of radiotherapy. At 4-month follow-up, there was no evidence of recurrence, and she remains symptomatically well. The various mechanisms of secondary localization are discussed.

Adenocarcinoma↗