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Biomedical subjects

J Jordan

Publications and source records attributed to J Jordan.

At least 91 records · Page 5Linked to original sources

Contrasting actions of pressor agents in severe autonomic failure.

BACKGROUND: Orthostatic hypotension is the most disabling symptom of autonomic failure. The choice of a pressor agent is largely empiric, and it would be of great value to define predictors of a response. PATIENTS AND METHODS: In 35 patients with severe orthostatic hypotension due to multiple system atrophy or pure autonomic failure, we determined the effect on seated systolic blood pressure (SBP) of placebo, phenylpropanolamine (12.5 mg and 25 mg), yohimbine (5.4 mg), indomethacin (50 mg), ibuprofen (600 mg), caffeine (250 mg), and methylphenidate (5 mg). In a subgroup of patients, we compared the pressor effect of midodrine (5 mg) with the effect of phenylpropanolamine (12.5 mg). RESULTS: There were no significant differences in the pressor responses between patients with multiple system atrophy or pure autonomic failure. When compared with placebo, the pressor response was significant for phenylpropanolamine, yohimbine, and indomethacin. In a subgroup of patients, we confirmed that this pressor effect of phenylpropanolamine, yohimbine, and indomethacin corresponded to a significant increase in standing SBP. The pressor responses to ibuprofen, caffeine, and methylphenidate were not significantly different from placebo. Phenylpropanolamine and midodrine elicited similar pressor responses. There were no significant associations between drug response and autonomic function testing, postprandial hypotension, or plasma catecholamine levels. CONCLUSIONS: We conclude that significant increases in systolic blood pressure can be obtained in patients with orthostatic hypotension due to primary autonomic failure with phenylpropanolamine in low doses or yohimbine or indomethacin in moderate doses. The response to a pressor agent cannot be predicted by autonomic function testing or plasma catecholamines. Therefore, empiric testing with a sequence of medications, based on the risk of side effects in the individual patient and the probability of a response, is a useful approach.

Aged↗

Red cell membrane skeletal changes in marathon runners.

Hemolysis in endurance exercise may be related to structural changes in red blood cell (RBC) membrane skeletal proteins. To test this hypothesis, we studied 13 male subjects before and after a marathon race. RBC membrane skeletons were observed with scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Plasma haptoglobin was measured. RBCs were affixed on poly-l-lysine coated glass supports for SEM and copper grids with formvar were prepared for TEM. Cytoplasmatic materials and lipid membranes were extracted with Triton-X-100 solution. TEM specimens were negatively stained and air dried. For SEM, the remaining RBC membrane skeletons were fixed, postfixed and sputtered with platinum. RBC membrane skeletal areas on SEM micrographs were measured by digitizer table planimetry. No RBC changes were observed with TEM. On the other hand, SEM showed disrupted RBC membrane skeletons. Furthermore, there appeared to be a loss of membrane material in RBC after the race, compared to RBC before the race. RBC membrane skeletal areas were increased by 30% (p<0.01). Hemolysis was indicated by a 57% decrease in plasma haptoglobin values (p<0.001). Thus, structural changes in RBC membrane skeletons occur after a marathon race. These changes can be identified with SEM but not with TEM. They may be related to increased susceptibility to chemical and physical stress and may contribute to hemolysis in endurance exercise.

Adult↗

Minocycline-induced hepatitis with autoimmune features and neutropenia.

Minocycline can cause various types of hepatotoxicity. We report an 18-year-old male who developed a delayed onset of minocycline-induced cholestatic hepatitis with autoimmune features and neutropenia. He responded to withdrawal of the drug and a short course of corticosteroids. If minocycline is to be administered, then periodic monitoring for hepatoxicity is recommended.

Acne Vulgaris↗

Assessing local health needs in primary care: understanding and experience in three English districts.

BACKGROUND: Assessing the health needs of a local population has been promoted as a key component in effective targeting of healthcare services and quality improvement. The understanding and experience of assessing health needs in general practice were investigated in three English districts. AIM: To identify the issues surrounding the potential for assessing health needs in primary care. METHOD: Postal survey of 347 general practices in three health authorities. Telephone interviews with a random stratified sample of 35 general practitioners. RESULTS: Although most practices identified assessing health needs as important, it is clear that this identification was typically based on an understanding of assessing needs as primarily focused on individual patient care, based on clinical priorities and involving practice held data. Most practices had not undertaken local consultation, whatever their understanding of assessing health needs. The few practices which had completed population oriented, proactive assessment of needs considered it to have led to tangible improvements in clinical or practice management. Overall, there was apparent confusion over the nature and purpose of assessing needs, although the principled aims and objectives of a population oriented, proactive component to primary care were generally upheld. The need for additional resources and support was identified. In four out of the five cases where specifically population based assessment of health needs had been undertaken, the local public health department had been involved. CONCLUSION: The value of the concept of assessing health needs in primary care holds considerable uncertainty and ambivalence. The findings from this study show that any attempts to promote assessing needs into primary care which focus either primarily or exclusively on the provision of "education" are unduly simplistic. More fundamental questions about the perceived relevance and opportunities for assessing health needs should be considered if primary care groups are to meet future commissioning challenges.

Community Health Planning↗

N(N)-nicotinic blockade as an acute human model of autonomic failure.

Pure autonomic failure has been conceptualized as deficient sympathetic and parasympathetic innervation. Several recent observations in chronic autonomic failure, however, cannot be explained simply by loss of autonomic innervation, at least according to our current understanding. To simulate acute autonomic failure, we blocked N(N)-nicotinic receptors with intravenous trimethaphan (6+/-0.4 mg/min) in 7 healthy subjects (4 men, 3 women, aged 32+/-3 years, 68+/-4 kg, 171+/-5 cm). N(N)-Nicotinic receptor blockade resulted in near-complete interruption of sympathetic and parasympathetic efferents as indicated by a battery of autonomic function tests. With trimethaphan, small postural changes from the horizontal were associated with significant blood pressure changes without compensatory changes in heart rate. Gastrointestinal motility, pupillary function, saliva production, and tearing were profoundly suppressed with trimethaphan. Plasma norepinephrine level decreased from 1.1+/-0.12 nmol/L (180+/-20 pg/mL) at baseline to 0.23+/-0.05 nmol/L (39+/-8 pg/mL) with trimethaphan (P<.001). There was a more than 16-fold increase in plasma vasopressin (P<.01) and no change in plasma renin activity. We conclude that blockade of N(N)-cholinergic receptors is useful to simulate the hemodynamic alterations of acute autonomic failure in humans. The loss of function with acute N(N)-cholinergic blockade is more complete than in most cases of chronic autonomic failure. This difference may be exploited to elucidate the contributions of acute denervation and chronic adaptation to the pathophysiology of autonomic failure. N(N)-Cholinergic blockade may also be applied to study human cardiovascular physiology and pharmacology in the absence of confounding baroreflexes.

Adult↗

Uncoupling of the baroreflex by N(N)-cholinergic blockade in dissecting the components of cardiovascular regulation.

Systemic administration of adrenergic agonists and nitric oxide donors is used extensively to determine cardiovascular receptor sensitivity. Conclusions regarding receptor sensitivity in the presence of the baroreflex may be misleading. In 8 normal volunteers, we determined the heart rate and blood pressure changes after incremental bolus doses of isoproterenol, phenylephrine, and sodium nitroprusside before and during neuronal nicotinic cholinergic (N(N)-cholinergic) blockade with trimethaphan. Results are given as median (25th/75th percentile). With trimethaphan, the baroreflex slope (as determined by bolus doses of nitroprusside and phenylephrine) decreased from 24 (22/26) to 0.00 (0.00/0.09) ms/mm Hg (P<0.01). The dose of isoproterenol that decreased systolic blood pressure (SBP) 12.5 mm Hg changed from 0.61 (0.51/5.3) to 0.17 (0.12/0.21) microg (P<0.01); the dose required to increase heart rate 12.5 bpm changed from 0.22 (0.17/0.41) to 0.74 (0.33/2.3) microg (P<0.01). The dose of nitroprusside required to decrease SBP 12.5 mm Hg changed from 2.3 (1.3/3.4) to 0.18 (0.14/0.24) microg/kg (P<0.01). The dose of phenylephrine required to increase SBP 12.5 mm Hg changed from 135 (110/200) to 16 (10/30) microg (P<0.01). We conclude that the efferent arc of the baroreflex can be completely interrupted with N(N)-cholinergic blockade. Estimation of adrenoreceptor sensitivity and sensitivity to nitric oxide donors by systemic administration of agonists is severely confounded by baroreflexes. Uncoupling of the baroreflex by N(N)-cholinergic blockade may be a useful method to obtain an integrated measure of adrenergic receptor sensitivity and sensitivity to nitric oxide donors in humans. This approach would permit the comparison of normal and abnormal physiological states without the "noise" of baroreflex buffering.

Adrenergic beta-Agonists↗

Raised cerebrovascular resistance in idiopathic orthostatic intolerance: evidence for sympathetic vasoconstriction.

Patients with idiopathic orthostatic intolerance (IOI) exhibit symptoms suggestive of cerebral hypoperfusion and an excessive decrease in cerebral blood flow associated with standing despite sustained systemic blood pressure. In 9 patients (8 women and 1 man aged 22 to 48 years) with IOI, we tested the hypothesis that volume loading (2000 cc normal saline) and alpha-adrenoreceptor agonism improve systemic hemodynamics and cerebral perfusion and that the decrease in cerebral blood flow with head-up tilt (HUT) could be attenuated by alpha-adrenoreceptor blockade with phentolamine. At 5 minutes of HUT, volume loading (-20+/-3.2 bpm) and phenylephrine (-18+/-3.4 bpm) significantly reduced upright heart rate compared with placebo; the effect was diminished at the end of HUT. Phentolamine substantially increased upright heart rate at 5 minutes (20+/-3.7 bpm) and at the end of HUT (14+/-5 bpm). With placebo, mean cerebral blood flow velocity decreased by 33+/-6% at the end of HUT. This decrease in cerebral blood flow with HUT was attenuated by all 3 interventions. We conclude that in patients with IOI, HUT causes a substantial decrease in cerebrovascular blood flow velocity. The decrease in blood flow velocity with HUT can be attenuated with interventions that improve systemic hemodynamics and therefore decrease reflex sympathetic activation. Moreover, alpha-adrenoreceptor blockade also blunts the decrease in cerebral blood flow with HUT but at the price of deteriorated systemic hemodynamics. These observations may suggest that in patients with IOI, excessive sympathetic activity contributes to the paradoxical decrease in cerebral blood flow with upright posture.

Adrenergic alpha-Agonists↗

[Mycosis infection (candidiasis) of the lingual thyroid gland].

The authors present a case of 60-year-old woman who suffered from a mycosis (Candidosis) infection of the ectopic lingual thyroid gland. Intensive inflammatory process caused enlargement of lingual goiter and dysphagia occurred consequently. Right diagnosis was made after scyntygraphic examination (the presence of lingual thyroid gland only), as well as histopathological and microbiological examinations which revealed the presence of Candida forms. Recovery was achieved after 5 weeks of antifungal treatment--Diflucan during a 2-week initial period, then followed by 3 weeks of local treatment with nystatin.

Candidiasis↗

[Laryngological aspects of treatment of male-female transsexuals].

The authors discuss laryngologist's participation in the adapting treatment of transsexuals of M/F type, including reduction of laryngeal prominence of thyroid cartilage, voice rehabilitation and nose operation. Literary reference is presented in the paper, as well as a case of a 27-year-old patient a transsexual of M/F type, in whom the prominence of thyroid cartilage was removed. Ethic and legal aspects of that management are also demonstrated.

Adult↗

Human parvovirus B19: prevalence of viral DNA in volunteer blood donors and clinical outcomes of transfusion recipients.

BACKGROUND AND OBJECTIVES: Blood donor units are not screened for human parvovirus B19 (B19) even though it can be acquired via blood products. We estimated the prevalence of B19 in a US volunteer blood donor population and determined the clinical outcomes of transfusion recipients. MATERIALS AND METHODS: Donor units were screened for B19 DNA by PCR, and positive units analyzed by EIA for B19 Ig. Unit usage was determined and recipient chart review conducted. RESULTS: B19 DNA was detected in 11/9, 568 allogeneic units (0.1%), of which 3 had no measurable B19 Ig. One individual developed anemia consistent with B19 infection after receiving a DNA+ unit lacking B19 Ig. CONCLUSIONS: The apparent low incidence of disease in patients transfused with B19 DNA+ components may be due to coexistence of neutralizing antibodies in donors and/or recipients.

Anemia↗

[Merkel cell carcinoma of the auricle].

A case of a 80-year-old woman suffering from Merkel cell carcinoma of the auricle with regional cervical lymph nodes metastases has been described. Surgical treatment (tumour and regional lymph nodes dissection) was applied at first. Metastasis to one lymph node was established in postoperative histological examination. Chemotherapy (farmorubicin, cyclophosphamide, vincristine) in 3 cycles was applied within 2 months. In spite of the above, 4 months after tumour excision, metastatic lymph node manifested in the neck. Combined treatment, radical neck dissection and radiotherapy was applied then.

Aged↗

Mutant superoxide dismutase-1-linked familial amyotrophic lateral sclerosis: molecular mechanisms of neuronal death and protection.

Mutations in human Cu/Zn superoxide dismutase-1 (SOD) cause approximately 20% of cases of familial amyotrophic lateral sclerosis (FALS). We investigated the mechanism of mutant SOD-induced neuronal degeneration by expressing wild-type and mutant SODs in neuronal cells by means of infection with replication-deficient recombinant adenoviruses. Expression of two FALS-related mutant SODs (A4V and V148G) caused death of differentiated PC12 cells, superior cervical ganglion neurons, and hippocampal pyramidal neurons. Cell death included many features typical of apoptosis. Death could be prevented by copper (Cu2+) chelators, Bcl-2, glutathione, vitamin E, and inhibitors of caspases. Mutant SOD-expressing PC12 cells had higher rates of superoxide (O2-) production under a variety of conditions. The results support the hypothesis that mutant SOD induced-neurodegeneration is associated with disturbances of neuronal free radical homeostasis.

Adenoviridae↗

Preemption in tobacco control. Review of an emerging public health problem.

OBJECTIVE: To describe the nature, extent, and public health significance of state legislation that preempts the local regulation of tobacco. DATA SOURCES: A computerized database of local tobacco control ordinances, state tobacco control laws, preemption bills introduced during the 1996 state legislative session, articles obtained through a MEDLINE search (1984-1996) using the key word "preemption" or identified from bibliographies of these articles, public opinion surveys, and newspaper articles. STUDY SELECTION: All identified data sources were used. DATA EXTRACTION: Content analyses of preemption bills and state laws were conducted independently by multiple observers. DATA SYNTHESIS: There has been a striking increase in the adoption of local tobacco control ordinances during the past decade; by the end of 1995, approximately 1006 communities had enacted a local tobacco control ordinance. In response, the tobacco industry has advanced legislation in 29 states that preempts local authority to regulate tobacco. During the 1996 state legislative session alone, 26 bills containing preemption were introduced, and 2 were enacted. Emerging trends in the tobacco industry's strategy to advance preemption laws include (1) amending legitimate tobacco control bills to preempt local tobacco regulation, (2) using the Synar amendment as a vehicle to advance preemption, and (3) promoting "superpreemption" bills that eliminate all local control of tobacco policy. CONCLUSIONS: Preemption of local tobacco regulation is an important tobacco industry strategy that undermines the public's health. Preventing the enactment of new preemption laws and repealing existing ones should become a public health priority.

Commerce↗

Moderate exercise leads to decreased expression of beta1 and beta2 integrins on leucocytes.

Intravascular adhesion of leucocytes plays a role in the pathogenesis of acute and chronic vascular disease. Regular aerobic exercise seems to protect against vascular disease. Since leucocyte adhesion is mediated by integrins, we tested the hypothesis that surface expression of the integrin adhesive receptors LFA-1 (cd11a/cd18), MAC-1 (cd11b/cd18), gp 150/95 (cd11c/cd18), and VLA-4 (cd29/cd49) is decreased by moderate endurance exercise. Surface expression of integrins was measured by FACS analysis in 19 healthy subjects (16 males, 3 females, 36.6 +/- 8.7 years, 177.1 +/- 7.5 cm, 70.3 +/- 8.1 kg) before and after submaximal exercise (3 h run) using monoclonal antibodies against cd11a, cd11b, cd11c, cd18, cd29 and cd49. In addition, we compared resting integrin expression in this group with a group of sedentary subjects (19 males, 6 females, 29.3 +/- 5.3 years). White blood cell count increased from 5300 ml(-1) to 9740 ml(-1) during exercise (P < 0.001). Nevertheless, the expression (indicated by the mean log fluorescence) of cd11a (94 +/- 24 vs. 78 +/- 14) and cd18 (128 +/- 31 vs. 102 +/- 21) on lymphocytes and of cd11a (104 +/- 25 vs. 85 +/- 16), cd11c (497 +/- 171 vs. 408 +/- 126) cd29 (109 +/- 16 vs. 89 +/- 16), cd49 (69 +/- 8 vs. 54 +/- 11) on monocytes was decreased after exercise (all P < 0.05). In contrast, integrin expression on granulocytes was not altered by exercise. Comparison of exercising and sedentary subjects showed a significantly decreased expression of integrins in exercising subjects. Our results demonstrate that moderate exercise leads to decreased expression of integrin receptors on leucocytes. This decreased expression of adhesion molecules may result in decreased adhesion and infiltration of leucocytes into the vessel wall. This phenomenon may play a role in the beneficial effect of moderate exercise in prevention of acute and chronic vascular disease.

Adult↗

Bone morphogenetic proteins: neurotrophic roles for midbrain dopaminergic neurons and implications of astroglial cells.

Bone morphogenetic proteins (BMPs) are members of the transforming growth factor beta (TGF-beta) superfamily that have been implicated in tissue growth and remodelling. Recent evidence suggests that several BMPs are expressed in the developing and adult brain. Specifically, we show that BMP 2 and BMP 6 are expressed in the developing midbrain floor of the rat. We studied potential neurotrophic effects of BMPs on the in vitro survival, transmitter uptake and protection against MPP+ toxicity of mesencephalic dopaminergic neurons cultured from the embryonic midbrain floor at embryonic day (E) 14. At 10 ng/ml and under serum-free conditions, most BMPs promoted the survival of dopaminergic neurons visualized by tyrosine hydroxylase immunocytochemistry during an 8-day culture period, but to varying extents (relative potencies: BMP 6 = 12 > 2, 4, 7). BMPs 6 and 12 were as effective as fibroblast growth factor-2 (FGF-2) and glial cell line-derived neurotrophic factor, promoting survival 1.7-fold compared with controls. BMPs 9 and 11 were not effective. Dose-response curves revealed an EC50 for BMPs 2, 6 and 12 of 2 ng/ml. BMPs 2, 4, 6, 7, 9 and 12 also promoted DNA synthesis and astroglial cell differentiation, visualized by 5-bromodeoxyuridine (BrdU) incorporation and glial fibrillary acidic protein (GFAP) immunocytochemistry respectively. Suppression of cell proliferation and subsequent maturation of GFAP-positive cells by 5-fluorodeoxyuridine or aminoadipic acid abolished the neuron survival-promoting effect of BMP 2. This suggests that BMPs, like other non-TGF-beta factors affecting dopaminergic neuron survival, act indirectly, probably by stimulating the synthesis and/or release of glial-derived trophic factors. BMP 6 and BMP 7 also increased the uptake of [3H]dopamine without affecting the uptake of [3H]5-hydroxytryptamine and [3H]GABA, underscoring the specificity of the trophic effect. We conclude that several BMPs share a neurotrophic capacity for dopaminergic midbrain neurons with other members of the TGF-beta superfamily, but act indirectly, possibly through glial cells.

1-Methyl-4-phenylpyridinium↗

The hypertension of autonomic failure and its treatment.

We studied the incidence and severity of supine hypertension in 117 patients with severe primary autonomic failure presenting to a referral center over a 9-year period. Patients were uniformly characterized by disabling orthostatic hypotension, lack of compensatory heart rate increase, abnormal autonomic function tests, and unresponsive plasma norepinephrine. Fifty-four patients had isolated autonomic impairment (pure autonomic failure). Sixty-three patients had central nervous system involvement in addition to autonomic impairment (multiple-system atrophy). Patients were studied off medications, in a metabolic ward, and on a controlled diet containing 150 mEq of sodium. Fifty-six percent of patients had supine diastolic blood pressure > or =90 mm Hg. The prevalence of hypertension was slightly greater in females (63%) than in males (52%). Potential mechanisms responsible for this hypertension were investigated. No correlation was found between blood volume and blood pressure. Similarly, plasma norepinephrine (92+/-15 pg/mL) and plasma renin activity (0.3+/-0.05 ng/mL per hour) were very low in the subset of patients with pure autonomic failure and supine hypertension (mean systolic/diastolic pressure, 177 +/- 6/108 +/- 2 mm Hg, range 167/97 to 219/121). Supine hypertension represents a challenge in the treatment of orthostatic hypotension. We found these patients to be particularly responsive to the hypotensive effects of transdermal nitroglycerin. Doses ranging from 0.025 to 0.1 mg/h decreased systolic blood pressure by 36+/-7 mm Hg and may effectively treat supine hypertension overnight, but the dose should be individualized and used with caution.

Aged↗