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PubMed2006

Telemetric recording of intrapleural pressure.

BACKGROUND: Monitoring of intrapleural pressure (IPP) is used for evaluation of lung function in a number of pathophysiological conditions. We describe a telemetric method of non-invasive monitoring of the IPP in conscious animals intermittently or continuously for a prolonged period of time. MATERIALS AND METHODS: After IACUC approval, six mongrel dogs were used for the study. After sedation, each dog was intubated and anesthetized using 0.5% Isoflurane. A telemetric implant model TL11M2-D70-PCT from Data Science International was secured subcutaneously. The pressure sensor tip of the catheter from the implant was inserted into the pleural space, and the catheter was secured with sutures. The IPP signals were recorded at a sampling rate of 100 points/second for 30 to 60 min daily for 4 days. From these recordings, the total mean negative IPP (mmHg), and the total mean negative IPP for a standard time of 30 min were calculated. In addition, the actual inspiratory and expiratory pressures were also measured from stable recording of the IPP waveforms. RESULTS: In six dogs, the total mean +/- SD negative IPP was -10.8 +/- 10.6 mmHg. After normalizing with respect to acquisition time it was -13.2 +/- 11.2 mmHg/min. The actual inspiratory pressure was -19.7 +/- 15.3, and the expiratory pressure was -11.0 +/- 12.9. CONCLUSIONS: Our study demonstrates that telemetric monitoring of IPP can be performed reliably and non-invasively in conscious experimental animals. The values for IPP in our study are compatible with the results of other investigators who used different methods of IPP measurement. Further work may show this method to be helpful in understanding the pathophysiology of various breathing disorders.

Animals↗
PubMedDate not supplied

The effect of uniform heating on the biomechanical properties of the intervertebral disc in a porcine model.

BACKGROUND CONTEXT: The use of minimally invasive lumbar intradiscal heating techniques, including intradiscal electro-thermal therapy (IDET), endoscopic radio-frequency annuloplasty, nucleoplasty and laser discectomy, for chronic lumbar discogenic pain and contained disc herniation has recently gained popularity. The purported therapeutic mechanisms of these interventions include subtotal nuclectomy, annular nociceptor ablation, and stabilization of the annular fibers. Basic science data elucidating the biomechanical and histomorphologic alterations of heat treatments on disc remain sparse. PURPOSE: The purpose of this study is to examine the effects of uniform heating on biomechanical properties and histomorphology of intervertebral disc tissues using a porcine model. STUDY DESIGN/SETTING: In a laboratory setting, porcine functional spinal units consisting of vertebra-nucleus pulposus-vertebra core and porcine hamstring tendons were harvested. Studies were performed on these tissue samples by uniformly heating the specimens in a constant temperature water bath. Ten porcine lumbar disc core and twenty-five porcine hamstring tendons were utilized as the subjects for this study. The effects of uniform heat treatments on disc core and hamstring tendon were measured for shrinkage, stiffness, and load to failure strength. Histomorphological study was also carried on the same specimen. METHODS: The porcine vertebra-nucleus pulposus-vertebra segments were cored to a uniform 1-cm diameter. The hamstring tendons were cut to uniform 1.2-inch lengths. The tendon specimens were divided into groups of five each and heated in constant temperature water baths of 60 degrees C, 65 degrees C, 70 degrees C, or 75 degrees C for 10 min. Unheated specimens served as controls. The disc core specimens were divided in two group of five each, and tested at room temperature or after immersion in a 70 degrees C bath. The shrinkage was monitored during immersion in the water bath. Biomechanical testing to failure was carried out using mechanical loading on an MTS servohydraulic testing machine operating under stroke control. Strength and stiffness of the tissue was determined. Histomorphology was studied by staining the specimen with hematoxylin and eosin (H&E), and examined under 200 times magnification. Non-heated controls were used for comparisons. RESULTS: The porcine hamstring tendons had no measurable shrinkage in specimens heated up to 65 degrees C. At temperatures above 65 degrees C, the shrinkage was concluded within 2 min of immersion and 70 degrees C appeared to be the optimal temperature, as temperatures higher than this did not demonstrate incremental effects. The disc core samples were heated to 70 degrees C (optimum temperature), and there appeared to be gross contraction of the disc core circumference to visual inspection, but no measurable lengthwise shrinkage could be appreciated. Histologically, the specimens demonstrated progressive loss of individual collagen fiber outline as the temperature increased. In the tendons, at 75 degrees C all of the fibers appear to be fused together, and the voids between individual collagen fibers were no longer present. Biomechanical testing revealed that the tendons undergo a substantial reduction in stiffness after heating. The mean tendon stiffness for the unheated specimens was 19,356 psi, while the corresponding value for the heated tendons was 1023 psi. These were significantly different using the paired t-test at p=0.0043. For the disc core samples, there was no significant difference in either stiffness (p=0.182) or failure strength (p=0.998) after heating. All failures occurred in mid-substance of the specimen. CONCLUSIONS: The application of uniform heating to nucleus pulposus disc core caused visible contraction of its circumference but not lengthwise shrinkage. The same heating shrinks the hamstring tendon and reduces its stiffness. Ultimate failure strength of the disc core specimen remains unchanged. The failure data was not obtainable for the tendon due to premature slippage from the fixation apparatus before failure. The results of this study fail to support a biomechanical justification for the application of uniform heat treatment to the whole intervertebral disc. Heating annulus fibrosus and nucleus pulposus separately to specific temperatures may have potential clinical benefits.

Animals↗
PubMed1999

An integrated view of pathophysiological models of schizophrenia.

Pathophysiological processes that underlie the profound neuropsychiatric disturbances in schizophrenia are poorly understood. However, the clinical course of the disease, and a number of clinical and basic science observations, provide direction for formulating pathophysiological models that could be empirically tested. For example, repeated psychostimulant administration to healthy subjects can induce psychotic symptoms, and acute stimulant challenge in schizophrenia patients can precipitate psychosis. Also, NMDA antagonists induce positive, negative, and cognitive schizophrenic-like symptoms in healthy volunteers and precipitate thought disorder and delusions in schizophrenia patients. These human studies provide support for the dopamine and NMDA receptor hypofunction hypotheses of schizophrenia. Well-documented effects of NMDA antagonists on dopamine systems provide a basis to integrate the dopamine and NMDA receptor hypofunction hypotheses. Furthermore, it has become apparent that prominent actions of antipsychotic drugs, especially those with 'atypical' properties, involve antagonism of behavioral, electrophysiological and brain metabolic effects produced by administration of NMDA receptor antagonists. A confluence of clinical and basic science data suggests that an early developmental insult, potentially involving reduced NMDA receptor function, could facilitate sensitization of dopamine systems, leading to the formal onset of schizophrenia in late adolescence and early adulthood. Although clearly speculative, this conceptual model is consistent with existing evidence and suggests lines of future experimental investigation.

Animals↗
PubMed1998

Chronopharmacological dependence of antihypertensive effects of the imidazoline-like drugs in stroke-prone spontaneously hypertensive rats.

In the present study we investigated the chronopharmacological dependence of dose-dependent hypotensive and cardiochronotropic effects of the imidazoline-like drugs (clonidine, rilmenidine and moxonidine) in stroke-prone spontaneously hypertensive rats (SHR-SP), using radio-telemetric system (Data Sciences, USA). The 24-h blood pressure, heart rate and locomotor activity profiles showed peak values during the rats' active phase during the night period. The degree of hypotensive and bradycardic effects of all drugs were most evident at this time and occurred in the absence of a change in locomotor activity. These studies show that clonidine, rilmenidine and moxonidine decrease blood pressure and heart rate in a time-dependent manner in SHR-SP. It was demonstrated that the degree and duration of hypotensive action of imidazoline-like drugs vary with the time of drug administration.

Animals↗
PubMed2000

Monitoring pig-to-primate cardiac xenografts with live Internet images of recipients and xenograft telemetric signals: histologic and immunohistochemical correlations.

BACKGROUND: Monitoring pig-to-primate cardiac xenografts is often difficult in awake and uncooperative primates. We investigated the possibility of monitoring xenotransplantation through Internet broadcasting of (1) continuous video images of transplant recipients and (2) xenograft telemetric signals detected by an implanted device. The telemetric readings were later compared with histology and immunohistochemistry for signs of rejection. METHODS: Heterotopic baboon-to-baboon (n = 2) and transgenic pig (human complement regulatory proteins CD59/DAF, n = 3; MCP, n = 1)-to-baboon transplants were performed with serial biopsies for hematoxylin-and-eosin staining and immunohistochemical detection of immunoglobulin M (IgM) and complement membrane attack complex (MAC) deposition. Baboon recipients were continuously monitored with a QuickCamPro digital camera, whereas grafts were monitored with a Data Science International implantable telemetric system. Video images and telemetric signals were broadcast over the Internet through a laptop computer. RESULTS: Baboon allografts remained healthy until explant on Day 14, whereas pig xenografts were rejected on Day 5, 6, 7, and 11. Telemetry of allografts and xenografts documented regular rhythm with an average heart rate of 80 to 120, but xenografts developed bradycardia and widened/dampened QRS complexes 24 to 48 hours before graft loss. Continuous video monitoring of recipient activities was vital in differentiating between graft arrhythmias and telemetric artifacts. Allograft biopsies showed little cellular infiltrate, whereas xenograft biopsies showed increasing IgM and MAC deposition, with extensive thrombi and myocardial damage 24 hours before cessation of cardiac activities. CONCLUSIONS: Combined video surveillance of recipient activities and graft telemetric signals is a useful method to continuously monitor abdominal cardiac grafts in large, uncooperative, awake primates. QRS-complex widening associated with progressive bradycardia correlated with histologic and immunohistochemical evidence of xenograft rejection.

Animals↗
PubMed1995

The NIH consensus development program.

The NIH CDCs are a highly visible, public forum to evaluate controversial medical technologies by synthesizing current medical science data. The consensus statements, although not intended as medical practice guidelines, may form part of the database preceding guideline formulation. It is difficult to assess the effect of the conferences on physician practice, in part reflecting the interference of the many other influences, medical and nonmedical, on physician behavior. Yet the program has had some success in influencing reimbursement policy for some technologies here and abroad and in influencing specialty organization policy, thereby indirectly affecting physician behavior. On the other hand, OMAR's dissemination activities have apparently been so successful that demand for CDC statements has more than doubled over the past five years, prompting OMAR to establish an information service (including fax and the Internet). And finally, the program has spawned consensus conferences throughout the world, including Canada, Western Europe, and Israel (Goodman & Baratz 1990).

Consensus Development Conferences, NIH as Topic↗
PubMed1990

Gay people and government security clearances. A social science perspective.

Lesbian and gay male applicants routinely are denied government security clearances or are subjected to unusually lengthy and intensive investigation. This article reviews social science data relevant to the principal justifications that have been offered for this policy and presents the following conclusions: (a) Lesbians and gay men are no more likely than heterosexuals to suffer from a personality disorder or emotional stress, or to be psychologically unstable; (b) lesbians and gay men are no more likely than heterosexuals to be unduly sensitive to coercion, blackmail, or duress; (c) lesbians and gay men are no more likely than heterosexuals to be unwilling to respect or uphold laws or regulations, or to be unreliable or untrustworthy. Three major flaws are discussed that underlie current government policies toward gay applicants for security clearances: (a) Groups rather than individuals are screened for undesirable characteristics; (b) applicants are rejected on the basis of problems created by government policies themselves; and (c) homosexual applicants are scrutinized according to criteria that are not applied similarly to heterosexual applicants. An alternative hypothesis, that experience with stigma actually may increase a gay applicant's ability to maintain secrecy, is discussed. Finally, some consequences of current policies are noted.

Female↗
PubMed1983

Specious causal attributions in the social sciences: the reformulated stepping-stone theory of heroin use as exemplar.

The claims based on causal models employing either statistical or experimental controls are examined and found to be excessive when applied to social or behavioral science data. An exemplary case, in which strong causal claims are made on the basis of a weak version of the regularity model of cause, is critiqued. O'Donnell and Clayton claim that in order to establish that marijuana use is a cause of heroin use (their "reformulated stepping-stone" hypothesis), it is necessary and sufficient to demonstrate that marijuana use precedes heroin use and that the statistically significant association between the two does not vanish when the effects of other variables deemed to be prior to both of them are removed. I argue that O'Donnell and Clayton's version of the regularity model is not sufficient to establish cause and that the planning of social interventions both presumes and requires a generative rather than a regularity causal model. Causal modeling using statistical controls is of value when it compels the investigator to make explicit and to justify a causal explanation but not when it is offered as a substitute for a generative analysis of causal connection.

Heroin Dependence↗
PubMed1997

The effects of triiodothyronine (T3) on heart rate, temperature and ECG measured with telemetry in freely moving mice.

We have set up a telemetry system and recorded heart rate, electrocardiogram (ECG), body temperature and the locomotor activity in awake freely moving mice. The telemetry system (DATA Sciences, St Paul, MN, USA) comprises a transmitter implanted in the peritoneal cavity and a receiver (RA1010) placed underneath the home cage. The signal from the transmitter includes the electrical activity of the heart and the body temperature. The results show that four days after the surgical procedure the mice have recovered and regained a clear circadian rhythm. The heart rate varied under baseline conditions between 432 and 618 beats min-1 and the body temperature between 35.1 and 37.7 degrees C (based on 60 min mean values). A clear time correlation between heart rate, body temperature and locomotor activity was found. As an evaluation of the method we injected T3 s.c. during a period of 4 days. Further, we were interested in whether it was possible to measure an integrated physiological response to T3 and further investigate the time course for the effect. After one day of treatment with triiodothyronine there was a significant increase in body temperature and locomotor activity. The increase in heart rate was seen after 2 days. The ECG recording revealed a significantly shortened QTend- and QRS-time. No significant difference in the PQ-time was found. This method may be of great importance in studies of genetically manipulated mice.

Animals↗
PubMed1999

The smell map: is there a commonality of odour perception?

The normal perception of odour quality is poorly understood, so formulating meaningful tests of olfaction is difficult. While tests of odour discrimination and odour detection threshold have helped quantify olfactory dysfunction, there are not yet predictive relationships between sensitivity to particular odours and particular forms of olfactory dysfunction. Using 11 commonly encountered odours, 20 normosmics performed similarity ratings of odour pairs. Multidimensional scaling, a standard behavioural sciences data analysis method, was used to explore the perceptual relationships between the odours based on their pair-wise similarity ratings. Smell maps were created for each individual as was a common or archetypal map which indicated a commonality in individuals' odour perception, far greater than chance alone (P < 10(-6)). A preliminary analysis of four hyposmics suggests that they do not conform to the normosmic archetype. Future studies assessing the relationship between odours in the archetype should improve the selection of odours to be included in tests of odour discrimination.

Adult↗
PubMed1999

Caring relationships with patients suffering from dementia--an interview study.

The aim of the study reported in this paper was to describe and analyse care-givers' caring relationships with patients suffering from dementia. The theoretical perspective was caring science. Data were collected through interviews with six care-givers in a ward for patients with severe dementia. From the qualitative analysis of the narratives, the following factors emerged as important for the caring relationships: 'touching', mutual 'confirmation', and the care-givers' 'values in the caring culture' in the ward. We conclude that communication skills are very important in a ward where patients with severe dementia reside, and that there is always a need for formulating the basic values. Theoretical education and clinical supervision are examples of means to improve competence and skills.

Adult↗
PubMed2001

Telemetric monitoring of adrenocorticotrophin-induced hypertension in mice.

1. The mouse is the animal of choice for studies involving genetic manipulation and transgenic and knockout mice are valuable tools for physiological studies. We have studied adrenocorticotrophin (ACTH)- and steroid-induced hypertension in both rat and humans. The aim of the present study was to develop a model of ACTH-induced hypertension in the mouse and to assess a chronically implanted telemetric device for measurement of blood pressure (BP). 2. Male Swiss Outbred and Quackenbush Swiss (QS) mice (35-45 g) were implanted with TA11PA-C20 BP devices (Data Sciences International, St Paul, MN, USA) under isoflurane anaesthesia. Seven to 10 days later, mice were monitored telemetrically for baseline BP for 4 days. Mice were then randomly allocated to: (i) sham treatment with normal saline s.c.; or (ii) ACTH at 500 microg/kg per day, s.c. Mice were monitored 24 h/day for 10 days. 3. Sham treatment (n = 7) did not affect BP (114 +/- 2/84 +/- 1 to 115 +/- 2/84 +/- 1 mmHg; P = NS). Adrenocorticotrophin treatment (n = 5) raised BP from 112 +/- 7/82 +/- 4 to 138 +/- 3/104 +/- 4 mmHg, which was significantly different from sham treatment (P = 0.0021 for systolic BP; P < 0.0001 diastolic BP). The increase in BP with ACTH was comparable with that seen in previous studies in humans, sheep and rat. Sham and ACTH-treated animals each lost 3% bodyweight. 4. Administration of ACTH (500 microg/kg per day) raises BP in two strains of mice, measured using a telemetry system. This model will allow the selective use of transgenic and/or knockout mice to further elucidate the mechanism of ACTH- and steroid-induced hypertension.

Adrenocorticotropic Hormone↗
PubMed2002

Observations on the growth of loose bodies in joints.

The categorization, origin, natural history, and histopathology of loose bodies in joints are well described in the literature. Clinical and basic science data have indirectly concluded that loose bodies grow over time; however, to date, there is no clearly documented published clinical example. This case report demonstrates the dramatic enlargement of 2 osteochondral loose bodies in a patient's knee over the course of a decade. The loose bodies possess a large number of viable cells; and growth appears to have occurred through encapsulation of the niduses by multiple layers of fibrocartilagenous tissue, thus confirming the findings of earlier studies.

Adult↗
PubMed2001

Long-term changes in Serengeti-Mara wildebeest and land cover: pastoralism, population, or policies?

Declines in habitat and wildlife in semiarid African savannas are widely reported and commonly attributed to agropastoral population growth, livestock impacts, and subsistence cultivation. However, extreme annual and shorter-term variability of rainfall, primary production, vegetation, and populations of grazers make directional trends and causal chains hard to establish in these ecosystems. Here two decades of changes in land cover and wildebeest in the Serengeti-Mara region of East Africa are analyzed in terms of potential drivers (rainfall, human and livestock population growth, socio-economic trends, land tenure, agricultural policies, and markets). The natural experiment research design controls for confounding variables, and our conceptual model and statistical approach integrate natural and social sciences data. The Kenyan part of the ecosystem shows rapid land-cover change and drastic decline for a wide range of wildlife species, but these changes are absent on the Tanzanian side. Temporal climate trends, human population density and growth rates, uptake of small-holder agriculture, and livestock population trends do not differ between the Kenyan and Tanzanian parts of the ecosystem and cannot account for observed changes. Differences in private versus state/communal land tenure, agricultural policy, and market conditions suggest, and spatial correlations confirm, that the major changes in land cover and dominant grazer species numbers are driven primarily by private landowners responding to market opportunities for mechanized agriculture, less by agropastoral population growth, cattle numbers, or small-holder land use.

Animals↗
PubMed2004

Hemodynamic effects of the nitric oxide donor DETA/NO in mice.

(Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA/NO) is a recently synthesized member of NO-releasing, polyamine zwitterions, the so-called NONOates, that spontaneously liberate NO in aqueous solutions. The aim of this study was to determine the hemodynamic effects of DETA/ NO in normotensive and hypertensive mice. Male Swiss Outbred mice were implanted with TA11PA-C20 blood pressure devices (Data Sciences International, USA). After recovery (7-10 days), blood pressure was monitored for 10 days while mice were receiving saline (0.1 ml/20 g/day, s.c.). Mice were then treated every four hours for 1 day with either DETA/NO 60 mg/kg i.p. or the inactive metabolite, diethylenetriamine 38 mg/kg (molar equivalent) i.p. After a 2 week wash-out period, mice were treated with adrenocorticotrophic hormone (ACTH: 500 microg/kg/day, s.c.) for 10 days and re-challenged with DETA/NO or diethylenetriamine. Results were expressed as mean +/- SEM. After 10 days of saline treatment, baseline systolic and diastolic blood pressure (BP) were similar for animals subsequently receiving DETA/NO or the amine (123 +/- 1/95 +/- 3 and 124 +/- 1/92 +/- 0.2 mmHg) respectively. DETA/NO induced a profound fall in BP [Systolic: 74 +/- 4 mmHg (-40 +/- 3%); Diastolic: 46 +/- 4 mmHg (-52 +/- 4%)] and an increase in heart rate [729 +/- 33 bpm (32 +/- 2%)] within the first 80 minutes. Diethylenetriamine had no effect. ACTH treatment increased BP in both groups (137 +/- 16/108 +/- 12 and 161 +/- 1/142 +/- 1 mmHg) respectively. DETA/ NO induced a profound fall in blood pressure [Systolic: 92 +/- 11 mmHg (-32 +/- 7%); Diastolic: 68 +/- 10 mmHg (-35 +/- 10%)] and an increase in heart rate [613 +/- 36 bpm (18 +/- 6%)] within the first 80 minutes. Again diethylenetriamine had no significant effect. There was no significant effect on body weight with any treatment. Thus DETA/NO has potent blood pressure lowering effects in both normotensive and hypertensive mice.

Adrenocorticotropic Hormone↗
PubMed2004

Using MoBIoS' scalable genome join to find conserved primer pair candidates between two genomes.

MOTIVATION: For the purpose of identifying evolutionary reticulation events in flowering plants, we determine a large number of paired, conserved DNA oligomers that may be used as primers to amplify orthologous DNA regions using the polymerase chain reaction (PCR). RESULTS: We develop an initial candidate set by comparing the Arabidopsis and rice genomes using MoBIoS (Molecular Biological Information System). MoBIoS is a metric-space database management system targeting life science data. Through the use of metric-space indexing techniques, two genomes can be compared in O(mlog n), where m and n are the lengths of the genomes, versus O(mn) for BLAST-based analysis. The filtering of low-complexity regions may also be accomplished by directly assessing the uniqueness of the region. We describe mSQL, a SQL extension being developed for MoBIoS that encapsulates the algorithmic details in a common database programming language, shielding end-users from esoteric programming. AVAILABILITY: Available upon request from authors.

Arabidopsis↗
PubMed1999

Current and future directions for meniscus repair and replacement.

Torn meniscal cartilages and the consequences of missing meniscus tissue represent the major indications for operative arthroscopy of the knee. After recognizing the importance of the meniscus, clinicians made the shift away from complete meniscectomy to partial meniscectomy aided by the development of arthroscopic instrumentation. Despite extensive basic science data showing the importance of a complete meniscus for normal force transference, meniscus repair occurs in less than 10% of all meniscal tears found at arthroscopy. This paper will discuss the reasons for the common clinical approach and compare that approach with an aggressive approach of salvaging and replacing meniscus tissue, and will offer speculations about future directions for meniscus repair, reconstruction, and replacement.

Biotechnology↗
PubMed2000

Cardiac hypertrophy depends upon sleep blood pressure: a study in rats.

OBJECTIVE: The objective of this study was to determine whether cardiac hypertrophy in hypertensive rats could be reduced and normalized by intermittent reduction of blood pressure, and to determine whether left ventricular hypertrophy was related to 24 h workload or peak blood pressure responses. METHODS: Hypertension was created by the application of a 0.20 mm clip to the left renal artery. Blood pressure response was monitored using a telemetry system (Data Science International). Blood pressure was reduced for varying periods of the day by giving different doses of captopril in the drinking water or by intra-peritoneal administration. Cardiac size was measured by weighing the ventricles and factoring by the body weight to obtain a cardiac index. RESULTS: Captopril 75 mg/kg per day and 25 mg/kg per day in the drinking water administered between 1800 and 2000 h lowered the 24 h blood pressure more than captopril 15 mg/kg per day or 5 mg/kg per day intra-peritoneally given at 0800 h. Captopril 75 mg/kg per day and captopril 15 mg/kg per day (intra-peritoneal) caused regression of cardiac hypertrophy whereas the other doses had no effect The best predictor of the cardiac hypertrophy response was the blood pressure between 0800 and 1200 h (i.e. the sleeping blood pressure). Twenty-four hour cardiac work did not correlate with the response. CONCLUSION: Cardiac hypertrophy can be reduced by intermittent treatment of elevated blood pressure. It is also caused by intermittent elevation of blood pressure. It appears that the crucial factor is when these alterations in blood pressure take place. An elevated blood pressure during the sleeping hours causes left ventricular hypertrophy, whereas a normal blood pressure during the sleeping hours allows reduction. It is suggested that acute wall stress is the signal to initiate the events that lead to cardiac hypertrophy but this only occurs if the hormonal milieu is appropriate.

Animals↗