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Biomedical subjects

T Alexander

Publications and source records attributed to T Alexander.

At least 19 recordsLinked to original sources
PubMed2005

Ocular structure and function in an aged monkey with spontaneous diabetes mellitus.

Diabetes mellitus develops spontaneously in middle-aged, obese rhesus monkeys, thus making them a good model for examining the effects of co-morbid factors on the development of end-organ damage. Changes in structure and function in the eyes of one monkey who spontaneously developed type 2 diabetes are reported here. This animal had concomitant hypertension, high levels of triglycerides and serum cholesterol, and a low fraction of high-density lipoprotein. The eyes showed intraretinal hemorrhages and large areas of retinal capillary nonperfusion. Indo-cyanin green (ICG) angiography revealed a large area of non- or poorly perfused choriocapillaris in one eye, and immunohistochemistry showed loss of viable choriocapillaries in this region. Both basal laminar deposits and hard drusen were present on areas of Bruch's membrane adjacent to nonviable choriocapillaris. Blood flow via the nasal posterior ciliary arteries to this section of choroid was not detectable by color duplex Doppler ultrasound, indicating contribution of extraocular vascular disease to ischemia in this eye. There was a severe decline in number of photoreceptor inner and outer segments, and corresponding reductions in the multifocal electroretinogram (ERG), in the areas of choriocapillaris loss. The ganzfeld ERG indicated loss in both inner and outer retinal function. Much of the ganglion cell layer was absent throughout the retina, possibly reflecting the effect of diabetes as well as chronic open angle glaucoma; the latter diagnosis supported by elevated intraocular pressures and excavated optic disks. In summary, high resolution, enzyme histochemical and histopathological analyses of a diabetic hypertensive monkey retina and choroid after serial functional in vivo analyses have demonstrated the relationship between vascular dysfunction and visual function loss. Choroidal vascular dysfunction in both large and small vessels was associated with age-related macular degeneration-like changes in Bruch's membrane and photoreceptor degeneration.

Aging↗
PubMed2005

Mid term outcome and quality of life after aortic valve replacement in elderly people: mechanical versus stentless biological valves.

OBJECTIVE: To assess the benefit for patients older than 65 years of aortic valve replacement with stentless biological heart valves in comparison with mechanical valves. DESIGN: Multiple regression analysis of a retrospective follow up study. SETTING: Single cardiothoracic centre. PATIENTS: Between 1996 and 2001, 392 patients with a mean age of 74 years underwent aortic valve replacement with stentless Freestyle bioprostheses or mechanical St Jude Medical prostheses. MAIN OUTCOME MEASURE: Operative mortality and morbidity, postoperative morbid events, mid term survival, and New York Heart Association (NYHA) class improvement, and quality of life. RESULTS: No significant differences were found between patients receiving stentless biological valves and patients receiving mechanical prostheses. However, analysis of subgroups showed that patients older than 75 years with mechanical valves had an increased risk of major bleeding events (p = 0.007). Patients requiring anticoagulation by means of coumarin had a twofold increased risk of an impaired emotional reaction (p = 0.052). However, for patients who received a mechanical valve for severe combined aortic valve disease a survival advantage (p = 0.045) and a decreased risk of prolonged ventilation (p = 0.001) was observed. On the other hand, patients receiving a stentless bioprosthesis had an increased risk of a prolonged stay in intensive care (p = 0.04) and stroke (p = 0.01) if they had severely reduced cardiac function (NYHA class IV). CONCLUSIONS: Elderly people receiving stentless bioprostheses benefit emotionally because of the avoidance of coumarin. However, in patients with severe hypertrophied ventricles and extraordinary calcifications, stentless bioprostheses should be chosen with caution.

Aged↗
PubMed2003

Near-infrared flares from accreting gas around the supermassive black hole at the Galactic Centre.

Recent measurements of stellar orbits provide compelling evidence that the compact radio source Sagittarius A* (refs 4, 5) at the Galactic Centre is a 3.6-million-solar-mass black hole. Sgr A* is remarkably faint in all wavebands other than the radio region, however, which challenges current theories of matter accretion and radiation surrounding black holes. The black hole's rotation rate is not known, and therefore neither is the structure of space-time around it. Here we report high-resolution infrared observations of Sgr A* that reveal 'quiescent' emission and several flares. The infrared emission originates from within a few milliarcseconds of the black hole, and traces very energetic electrons or moderately hot gas within the innermost accretion region. Two flares exhibit a 17-minute quasi-periodic variability. If the periodicity arises from relativistic modulation of orbiting gas, the emission must come from just outside the event horizon, and the black hole must be rotating at about half of the maximum possible rate.

Journal Article↗
PubMed2002

A star in a 15.2-year orbit around the supermassive black hole at the centre of the Milky Way.

Many galaxies are thought to have supermassive black holes at their centres-more than a million times the mass of the Sun. Measurements of stellar velocities and the discovery of variable X-ray emission have provided strong evidence in favour of such a black hole at the centre of the Milky Way, but have hitherto been unable to rule out conclusively the presence of alternative concentrations of mass. Here we report ten years of high-resolution astrometric imaging that allows us to trace two-thirds of the orbit of the star currently closest to the compact radio source (and massive black-hole candidate) Sagittarius A*. The observations, which include both pericentre and apocentre passages, show that the star is on a bound, highly elliptical keplerian orbit around Sgr A*, with an orbital period of 15.2 years and a pericentre distance of only 17 light hours. The orbit with the best fit to the observations requires a central point mass of (3.7 +/- 1.5) x 10(6) solar masses (M(*)). The data no longer allow for a central mass composed of a dense cluster of dark stellar objects or a ball of massive, degenerate fermions.

Journal Article↗
PubMed2002

[Transillumination technique in difficult intubations in heart surgery].

OBJECTIVE: The avoidance of myocardial depression still remains the goal of the management for cardiosurgical patients, also when unexpected difficulties in intubation face the anaesthetist. Therefore the difficult intubation should be managed by a short and easy procedure which provides safe results. To analyse the use of transillumination technique with a lightwand device (Trachlight(R), Laerdale, USA) in case of unexpected difficult intubation is the aim of our report. Methods All cardiosurgical patients (NYHA II - IV) were included from Jan 1998 - Dec 2001. After failure of the first intubation attempt by means of direct laryngoscopy (with non-adjustable vocal cord level) this intubation was qualified as an difficult intubation. In all these cases a lightwand device (Trachlight(R), Laerdale, USA) was applicated. Success, duration of the procedure, blood pressure, heart rate were recorded. Results 195 patients (out of total 7406) who could not be directly intubated by laryngoscopy (vocal cord level and arytenoid cartilage not visible), were classified as a difficult intubation. During the first year 1998 the light guided intubation (LGI) was successful as secondary procedure in 94 %, 3 cases, in which LGI failed the intubation was performed by fiberoptic method or McCoy blade. From 1999 to 2001 all difficult intubation could be managed by light guided intubation. In all cases of unexpected difficult intubation the procedure of the light guided intubation took as less than 3 min. The directly measured arterial blood pressure elevated by 14 % in comparison with the pressure prior to the passage through the larynx. Discussion and Conclusions 1998 after sufficient familiarisation of staff with the light wand device the transillumination technique was introduced as an alternative of using the McCoy blade or of using the fiberoptic method in the case of difficult intubation. Short neck or obesity, which occur as main reasons for intubation problems are surprisingly easy to control by light wand device. Therefore the light guided intubation could be an alternative procedure for unexpected difficult intubation in the setting of adult cardiac anesthesia.

Aged↗
PubMed2001

Near-infrared spectrometric determination of di- and tripeptides synthesized by a combinatorial solid-phase method.

A new method based on near-infrared (NIR) spectrometry and partial least-squares analysis has been developed for the noninvasive and nondestructive determination of the identity and sequences of amino acid residues in di- and tripeptides. The di- and tripeptides were synthesized from six amino acids with similar structures (Gly, Ala, Leu, Met, Phe, Val) on two different polymer beads (bead with and without a linker) using the solid-phase peptide synthetic method. The developed NIR method is capable of determining the identity of sequences of these di- and tripeptides (with and without the Fmoc protecting group) directly on the polymer beads. It can distinguish not only dipeptides from tripeptides but also peptides with very similar structures (e.g., bead-Gly-Ala-Ala, bead-Gly-Ala-Phe, bead-Gly-Ala-Leu, bead-Gly-Ala-Val, and bead-Gly-Ala-Met). More importantly, the method is capable of distinguishing di- and tripeptides with the same amino acid residues but different sequences (e.g., bead-Gly-Leu-Val from bead-Gly-Val-Leu).

Combinatorial Chemistry Techniques↗
PubMed2001

Organ and species specificity in the stimulation of transitional epithelial cell growth by fibroblasts.

OBJECTIVES: Culture of transitional epithelium for urinary tract reconstruction has been problematic due, in part, to the dependence of urothelial cells on a basal layer of bladder fibroblasts for growth. In vitro studies on the effect of bladder, ureter, and intestinal fibroblast cocultures and conditioned media upon urothelial cell growth were conducted to better characterize the dependence of urothelial cells of fibroblasts. METHODS: Primary cultures of human and porcine bladder, ureter, and intestinal fibroblasts and bladder and ureter urothelial cells were established. The urothelial cells were incubated with fibroblasts in a coculture system and growth compared to that of individual fibroblast and urothelial cultures. Urothelium-specific medium was exposed to the fibroblast cultures for 6, 12, and 24 h. Urothelial cell growth in each of the fibroblast-conditioned media was evaluated. RESULTS: Coculture of human urothelial cells with human bladder and ureter fibroblasts yielded increased cell growth when compared to the cells in individual culture. This improvement was greatest for the bladder fibroblasts in coculture with bladder epithelial cells. The media exposed to bladder and ureter fibroblasts for 24 h significantly increased bladder and ureter urothelial growth compared to fresh medium. Coculture with intestinal fibroblasts and exposure to intestinal fibroblast conditioned media did not significantly stimulate urothelial cell growth. Similarly, coculture and conditioned media studies of porcine urothelial cells with porcine bladder and ureter fibroblasts (but not intestinal fibroblasts) yielded increased cell growth when compared to the cells in individual culture, particularly with bladder fibroblasts. However, human urothelial cells were not stimulated by porcine bladder and ureter fibroblast conditioned media, nor were porcine urothelial cells stimulated by human bladder and ureter fibroblast conditioned media. CONCLUSIONS: The ability of urinary fibroblasts to stimulate urothelial cell proliferation resides in an unidentified soluble factor secreted into the medium, independent of the presence of the fibroblasts. This factor is relatively organ and species-specific.

Animals↗
PubMed2000

Hexosamines stimulate leptin production in transgenic mice.

Hexosamine flux has been shown to mediate aspects of nutrient sensing in insulin sensitive tissues and has been hypothesized to represent a satiety signal that results in shunting of fuel toward storage as fat. It has been recently reported that in vitro treatment of fat and muscle cells with hexosamines and acute glucosamine infusion in intact rats stimulate leptin secretion. In order to investigate the effects of chronic, physiologic increases in hexosamine flux on leptin we have examined leptin mRNA and serum leptin in mice overexpressing the rate-limiting enzyme for hexosamine synthesis, GFA, in muscle and fat. Increased levels of UDP-N-acetylglucosamine, the principal end-product of the hexosamine pathway were seen in transgenic fat, consistent with the overexpression of GFA. After overnight fasting, the transgenic mice were hyperleptinemic compared to littermate controls (4.5+/-0.5 ng/ml in transgenic, 2.8+/-0.2 in control, p = 0.005) despite equal body weights. In the random-fed state, the leptin levels of control mice increased to 4.1+/-0.5 ng/ml (p = 0.01) whereas the leptin levels in the transgenics did not increase any further (3.7+/-0.4 ng/ml). Leptin mRNA levels were also increased in transgenic fat (2.7+/-0.6 in transgenic compared to 0.8+/-0.2 in control, arbitrary units normalized to actin, p < 0.007). Despite increased leptin, the transgenic animals did not have lower body fat content. We conclude that hexosamine flux in fat regulates leptin synthesis and secretion.

Adipose Tissue↗
PubMed1999

[Arterial myocardial revascularization in the 9th decade of life. Personal results and review of the literature].

The rate of the population being 80 years of age and even older, has an increasing tendency in the Federal Republic of Germany. In 1996, a total of 87,372 patients received surgery supported by the heart-lung-machine, 2,383 patients out of these (2.7%) were 80 years of age and older. In view of the limited life expectance, the arterial revascularization in this age category is faced with controverse discussions. We analysed our patients in relation to this aspect. Between January 1, 1995 and June 30, 1997, 4,338 patients underwent surgery supported by the heart-lung-machine. Hundred and fifty-five out of these (3.6%) were in the 9th decade of life. Seventy-seven patients out of the 155 (49.7%, 34 women, 43 men, 80 to 88 years old, mean: 82 years of age) underwent an isolated myocardial revascularization. We performed 55 (71%) elective, 16 (21%) urgent and 6 (8%) emergency surgeries. Twelve patients (15.6%) solely received venous bypasses (Group I), 65 (84.4%) additionally also received unilateral bypasses of the internal mammaria artery (IMA) (Group II). Three patients died at our facility (3.9%), 3 further patients died during the follow-up treatment in outlying hospitals, the in-patient mortality rate in Group I therefore presented a rate of 8.3%, in Group II 7.7% and in total, a rate of 7.8%. In 1996, the in-patient mortality rate could be reduced to 3.6%. The follow-up observation time ranged between 7 and 138 weeks (median 44 weeks). The survival rate for patients with an IMA-bypass after 1 year was 86.3%, after 2 years 77%, and for the entire collective 85.3% and 75%. Whereas 96% of the patients could pre-operatively be related to Class III or IV of the NYHA-classification, 55 of the 63 survivors (87%) belonged to Class I (6%) or II (81%). Two Group I patients (22.2%), 3 Group II patients (5.6%) and 7.9% of the total collective complained about repeated angina symptoms. The myocardial revascularization with the internal mammaria artery performed on patients in the 9th decade of life, achieves an acceptable morbidity and mortality compared to solely venous coronary bypasses. The more prolonged follow-up observation period will clarify, whether the arterial myocardial revascularization also proves to be the superior method in this age category.

Aged↗
PubMed1999

Simultaneous myocardial revascularization and aortic valve replacement: stentless versus stented bioprostheses.

Implantation of stentless aortic valve prostheses is more time-consuming than implantation of conventional stented bioprostheses. Simultaneous myocardial revascularization can result in a considerably prolonged operation time. We reviewed our patients with regard to surgical aspects in the specific patient cohorts. From April 1996 to April 1999, 303 patients were operated for aortic valve disease with or without concomitant coronary artery revascularization. Mean age was 75 years, ranging between 36 and 90 years. Using the Medtronic Freestyle valve, the following techniques of implantation were used: subcoronary technique, 163 patients, 61.5%; root inclusion technique, 7 patients, 3.5%; total root replacement, 30 patients, 15%. Total hospital mortality rate was 5.6%, reflecting age and concomitant disease of these patients. For isolated aortic valve replacement, the mortality rate was 4.7% and 6.7% for combined procedures. Coronary artery patients who are not suitable for stentless valve implantation owing to extensive aortic root calcification have a higher perioperative mortality rate. Compared with the isolated valve replacement and despite more extensive surgery and prolonged operative time, simultaneous myocardial revascularization in patients with stentless prostheses implantation can be performed without an increased risk.

Adult↗
PubMed1997

Adolescents report their need for and use of health care services.

PURPOSE: The goals of this study were to describe student access to health care services, identify populations of students who remained in need of health care services, and highlight particular unmet needs for health care identified by these adolescents. METHODS: Students in Grades 9-12 attending 50 schools in Oregon completed the Youth Risk Behavior Surveillance Survey (YRBS). Questions requesting adolescents to report their need for specific types of health care, and access to general and specific types of care were added to the core YRBS. Multivariate logistic regression analysis was used to determine independent relationships between student or community characteristics and health care access or unmet needs for care. RESULTS: Almost 14,000 adolescents completed surveys, of whom 75% reported visiting one or more health care provider within the last 12 months. Nineteen percent of adolescents reported that they had not received 1 or more of 10 specific types of care when needed in the last year. Females, some racial/ethnic minorities, rural, and sexually active adolescents were more likely to report unmet needs for health care. Most frequently, adolescents reported they needed but did not receive care for an illness (7%) or for personal or emotional problems (6%). In addition, about 400 (3%) students reported they needed birth control that they did not receive. CONCLUSIONS: A majority of high school-age adolescents had visited health care providers within the year prior to study. However, the number of adolescents who reported unmet specific health care needs within the same time period remained substantial.

Adolescent↗
PubMed1996

Continuing professional education: a challenge for rural health practitioners.

Health professionals in rural and remote areas of Australia are disadvantaged when accessing continuing education. Their geographical isolation influences attendance at seminars, workshops and even informal discussions with colleagues. This paper describes the strategies adopted to meet the continuing education needs of a group of health professionals working in diabetes education and discusses how other specialist areas can provide similar educational opportunities. The education programs for isolated health professionals involved in diabetes care in South Australia were created by a team, and the resources of their associated institutions. Formal working agreements were established to achieve the aim of relevant continuing education for rural health professionals and to ensure ongoing ventures. All programs have been positively received, and evaluations identify the need to develop other, related subjects. Future developments will further utilise advances in technology to extend access and add to the current modes of education delivery. It is the intention of this group to continue to develop practice-based subjects capable of meeting rural health practitioners' needs and thus enhance the quality of care in rural and remote communities.

Diabetes Mellitus↗
PubMed1994

Cardiovascular responses during static exercise. Studies in patients with complete heart block and dual chamber pacemakers.

BACKGROUND: During static exercise in normal subjects, the mean arterial pressure increases as a result of an increase in heart rate and thereby cardiac output with no significant change in stroke volume or systemic vascular resistance. We hypothesized that if one component of the blood pressure response to static exercise, ie, heart rate, were fixed, plasticity of the neural control mechanisms during exercise would allow for preservation of the blood pressure response by alternative mechanisms. METHODS AND RESULTS: Thirteen patients 20 to 68 years old with structurally normal hearts, complete heart block, and dual chamber pacemakers performed static exercise during three conditions: (1) normal dual chamber sensing and pacing mode, (2) heart rate fixed at the resting value obtained in the DDD mode of 78 +/- 4 beats per minute, and (3) heart rate fixed at the peak value obtained during exercise in the DDD mode of 94 +/- 4 beats per minute. Heart rate, blood pressure, and cardiac output were measured and stroke volume and systemic vascular resistance were calculated at rest and at 1 and 5 minutes during static one-leg extension at 20% of maximal voluntary contraction. The mean arterial pressures at rest and at 5 minutes were higher when the heart rate was fixed at the faster peak exercise heart rate. In the DDD mode, heart rate increased by 16 beats per minute and cardiac output by 1.1 L/min, with a resultant 25 mm Hg increase in mean arterial pressure at 5 minutes with no change in the stroke volume or systemic vascular resistance. In both fixed heart rate pacing modes, mean arterial pressure increased by 24 mm Hg when the heart rate was fixed at the resting heart rate and by 25 mm Hg when the heart rate was fixed at the faster peak exercise heart rate pacing modes associated with an increase in stroke volume, with similar increases in cardiac output. During static exercise there was no change in systemic vascular resistance from the resting value in any pacing mode. CONCLUSIONS: When heart rate is fixed in the presence of normal left ventricular function, the mean arterial pressure increases normally during static exercise because of an increase in stroke volume with no change in the systemic vascular resistance.

Adult↗
PubMed1993

One man's tough choices on prostate cancer.

It's the No. 2 cancer killer in men--and it will strike almost every male who lives long enough to get it. But when a seasoned science journalist was diagnosed with it, doctors gave him confusing and contradictory advice. In his painful journey through the maze, he learned that where doctors disagree--as they do over how to treat many life-threatening diseases--an educated patient can help educate them.

Clinical Protocols↗