Biomedical subjects

W R Martin

Publications and source records attributed to W R Martin.

At least 73 records · Page 4Linked to original sources

PubMed1992

Movement of the i.v. room to the postanesthesia care area: an alternative to an operating room satellite pharmacy.

The Jewish Hospital of St. Louis decided to combine the need for an operating room (OR) satellite pharmacy with the need to upgrade the existing intravenous (IV) room. This decision resulted in the movement of the move not only provided an upgraded IV room but its location allowed for direct access to the OR suites. The IV room can now provide the additional services of an OR satellite pharmacy. Cost savings estimates for a dedicated OR satellite pharmacy did not provide the hospital administration with the financial justification for the project. Only by combining the pharmacy's personnel and physical resources did the proposal become inviting enough for the hospital administration to support. The steps in the creation of the combined IV room/OR satellite pharmacy are presented.

Cost Savings↗

PubMed1992

Opioid and nicotinic analgesic and hyperalgesic loci in the rat brain stem.

The effects of (-)-nicotine and ethylketazocine (EKC) on the latency of a low-intensity thermally evoked tail avoidance response were evaluated at different midline mesencephalic, pontomedullary and medullary sites of conscious intact rats. Guide cannulae were implanted surgically at six anterior-posterior stereotaxic locations (AP, -4.4 to +2.8) and drugs were microinjected (0.5 microliter) at different depths in each region. The analgesic effects of naltrexone and mecamylamine were evaluated at those sites exhibiting sensitivity to the hyperalgesic actions of (-)-nicotine and EKC. Additional experiments evaluated the validity and reproducibility of the low-intensity thermally evoked tail avoidance response and a low intensity hot plate response in detecting hyperalgesia. The chemostimulation studies suggest that there are opioid and nicotinic hyperalgesic processes distributed throughout the dorsal regions of the posterior mesencephalic and pontomedullary brain stem. The relative hyperalgesic potency of (-)-nicotine appears to exhibit a gradient from the dorsal posterior mesencephalic tegmentum to the midmedullary region, whereas only analgesia was produced more rostrally, in the central gray, or caudally within the posterior medulla. Within regions intermediate between the dorsal posterior, mesencephalic tegmentum and posterior medulla, (-)-nicotine produced biphasic dose-response and time action curves. The effects of EKC were similar to those of (-)-nicotine at most sites although (-)-nicotine was 55 times more potent than EKC when administered in the most active hyperalgesic regions.2+ may differ from region to region.

Analgesia↗

PubMed1991

Assessing risk factors for transmission of infection.

Commonly used measures of effect, such as risk ratios and odds ratios, may be quite biased when used to assess the effect of factors that alter transmission risks given exposure to infected individuals. This is demonstrated in a simulation model involving a higher-risk behavior and a lower-risk behavior affecting the sexual transmission of human immunodeficiency virus. The bias arises because population contact patterns between higher-risk and lower-risk persons change their relative probabilities of exposure to an infected individual as an epidemic progresses. The assessment of contact patterns is thus central to risk assessment for contagious diseases. A new formulation of selective mixing presented here, together with a structured mixing specification of the social settings of contact, provides a theoretic framework for the investigation of contact pattern determinants.

Bias↗

PubMed1991

[Diagnosis of rare causes of upper gastrointestinal tract bleeding].

Possible errors in diagnosing rare sources of bleeding were analysed in 433 consecutive patients examined for upper gastrointestinal bleeding between May 1987 and June 1990. Rare lesions not necessarily recognizable as sources of bleeding were found in 14 patients (8 women and 6 men; mean age 66 [46-82] years). In 9 of the 14 the lesion was above the ligament of Treitz and thus accessible to routine esophagogastroduodenoscopy. Nonetheless, in 4 of these 9 cases the source of bleeding was not recognized at the first gastroscopy. They were all lesion in the region of the horizontal duodenum or Treitz's ligament (3 duodenal carcinomas, 1 aortoduodenal fistula). This finding indicates that, if the deep duodenum cannot be assessed with certainty in the initial gastroduodenoscopy, the region should be selectively studied endoscopically or radiologically before more invasive examinations are undertaken. In the remaining 5 of the 14 patients the source of bleeding was distal to Treitz's ligament. After the usual diagnostic tests (esophagogastroduodenoscopy, coloscopy, small intestine double-contrast imaging, angiography, scintigraphy) the sources of bleeding (angiodysplasias, jejunitis, enteritis) were confirmed in four patients by intraoperative ileo-jejunoscopy. In three of the latter cases bleeding did not recur after operative intervention, in one patient with multiple angiodysplasias severe bleeding recurred immediately after operation.

Aged↗

PubMed1991

Positron emission tomography in progressive supranuclear palsy.

Positron emission tomography with 6-[18F]fluoro-L-dopa (6-FD) provides in vivo information on the function of nigrostriatal dopaminergic neurons. We used 6-FD and positron emission tomography to investigate the integrity of the nigrostriatal system in seven patients with progressive supranuclear palsy. All patients had axial hypertonia, vertical gaze palsy, and parkinsonian features. Dementia, pyramidal signs, and ataxia were seen in varying proportions. We analyzed the scans with a graphic method to calculate a steady-state 6-FD uptake rate constant for the whole striatum. Results were compared with those obtained in seven age-matched controls. As a group, the patients with progressive supranuclear palsy had reduced 6-FD uptake constants. The 6-FD uptake constant correlated inversely with the duration of the disease. Normal positron emission tographic findings in one patient with the shortest duration of symptoms suggests that in early progressive supranuclear palsy, parkinsonism may relate to dysfunction distal to the dopaminergic neurons.

Aged↗

PubMed1991

Positron emission tomography suggests that the rate of progression of idiopathic parkinsonism is slow.

We performed sequential positron emission tomography scans with 6-[18F]fluoro-L-dopa in 9 patients with idiopathic parkinsonism and 7 age-matched normal control subjects to compare changes in the nigrostriatal dopaminergic pathway over time. The mean interval between the scans was 3.3 years for the group with idiopathic parkinsonism and 3.9 years for the control subjects. The scans were analyzed by calculating the ratio of striatal to background radioactivity. Both groups showed statistically significant reductions of striatal uptake over the interval. The rate of decrease was almost identical in each group (p = 0.6). We infer that the usual rate of loss of integrity of the dopaminergic nigrostriatal pathway in patients with idiopathic parkinsonism is slow and the rate of change between the two groups was comparable.

Adult↗

PubMed1991

Growth and differentiation of primary tracheal epithelial cells in culture: regulation by extracellular calcium.

Growth and differentiation of primary monkey tracheal epithelial (MTE) cells maintained on collagen gel substrata were studied in a defined serum-free culture medium containing 0.03 to 3.0 mM extracellular calcium. Cell attachment efficiency (40-60%) was not altered by different calcium levels. Growth of primary MTE cells on collagen gel substrata, which was vitamin A dependent, was enhanced 50% in the medium supplemented with high calcium (greater than 0.3 mM). High calcium medium also increased cell-cell interactions, formation of desmosomes, and multi-cell layering. The relative content of mucous cells, which were identified by a mucin-specific monoclonal antibody and the presence of mucus-secreting granules at the ultrastructural level, was greater in the high-calcium medium. Furthermore, the secretion of mucin into the medium, determined either by an ELISA or by the incorporation of 3H-glucosamine into mucous glycoprotein fractions, was also increased more than 5-fold in media containing high calcium content (greater than 0.6 mM). In contrast, MTE cells cultured in low calcium medium (less than 0.15 mM) were squamous-like with prominent tonofilaments, and their secretory product was mainly hyaluronate. These results demonstrate that media containing a high calcium content promote conducting airway epithelium to express mucous cell differentiation, while media with low calcium content promote squamous cell differentiation.

Animals↗

PubMed1991

Distribution of diazepam, nordiazepam, and oxazepam between brain extraneuronal space, brain tissue, plasma, and cerebrospinal fluid in diazepam and nordiazepam dependent dogs.

The compartmental distribution of diazepam (DZ) and nordiazepam (ND) and their metabolites was studied in DZ and ND dependent dogs. The levels of DZ, and ND and their metabolites were determined during the last week of stabilization in the extraneuronal brain space, in brain tissue, in plasma and in CSF. In these studies dependent dogs were anesthetized with pentobarbital and microdialysis probes were inserted bilaterally into the parietal cortex and perfused with artificial cerebrospinal fluid. Microdialysis probes were also used to determine the unbound parent drugs and their metabolites in plasma. The brain-plasma distribution of total ND and oxazepam (OX) is about equal in ND dependent dogs but in DZ dependent dogs total ND and OX are about 2-fold higher in brain than in plasma. The levels of DZ, ND, and OX in the extraneuronal brain space are similar to their unbound levels in plasma. These data suggest that the concentration of free benzodiazepines in plasma is a good approximation of the concentration in the vicinity of the membrane receptors in the dependent dogs.

Animals↗

PubMed1991

Pharmacokinetics and metabolism of halazepam in naive and dependent dogs.

The pharmacokinetic profiles of halazepam (HL) and its metabolites, desmethyldiazepam (DMDZ), oxazepam (OX), 3-hydroxyhalazepam (OH-HL), and conjugates of oxazepam (OX-CONJ) and 3-hydroxyhalazepam (OH-HL-CONJ) were studied in 4 naive dogs following single intravenous (2 mg/kg) and oral (112.5 mg/kg) administrations of HL and in 5 dependent dogs chronically dosed with HL (450 mg/kg/day q.i.d.). HL is rapidly metabolized to DMDZ as the principal metabolite but appreciable levels of HL, OX and OH-HL were measured in plasma and the brain tissue. High levels of conjugated metabolites were measured in plasma. The steady-state plasma concentrations of HL and its unconjugated metabolites can be predicted from the single dose study. Halazepam does not serve as a simple prodrug for DMDZ in producing physical dependence in dogs.

Animals↗

PubMed1991

A comparison of the physical dependence inducing properties of flunitrazepam and diazepam.

Dogs dosed chronically (4-7 weeks) with oral flunitrazepam (7.6 mg/kg/day) or diazepam (24-36 mg/kg/day) administered in 4 equally divided doses had dose-related flumazenil precipitated benzodiazepine abstinence scale scores (BPAS) of comparable intensities despite the fact that plasma levels of flunitrazepam and its metabolites were much lower than nordiazepam levels in the diazepam-dependent dog. Both groups of dependent dogs had clonic and tonic-clonic seizures after oral and IV flumazenil. Precipitated abstinence signs persisted longer in the diazepam than in the flunitrazepam-dependent dogs. Differences in the pharmacokinetics of the drugs of dependence, their metabolites, and their interactions at receptor sites offer a partial explanation for the high level of dependence seen in the flunitrazepam dog. The finding that the estimated plasma free concentration of flunitrazepam and its metabolites is equal to or greater than that of diazepam and its metabolites together with the fact that flunitrazepam has a higher affinity for the benzodiazepine receptor than either diazepam, nordiazepam or oxazepam can explain why the intensity of the precipitated abstinence syndrome is comparable in flunitrazepam- and diazepam-dependent dogs. Although the flumazenil-induced precipitated abstinence syndromes observed in flunitrazepam- and diazepam-dependent dogs differed qualitatively they did not differ quantitatively. It is therefore concluded from these data that the doses of flunitrazepam and diazepam, chosen for producing comparable degrees of weight loss during dose escalation, did not differ in the degree of physical dependence that they produced in the dog.

Animals↗

PubMed1991

Chronic administration of and dependence on halazepam, diazepam, and nordiazepam in the dog.

Halazepam administered chronically to dogs in oral doses of 180 and 450 mg/kg/day produced physical dependence which was revealed by a flumazenil precipitated abstinence syndrome and measured by the Nordiazepam Precipitated Abstinence Scale score (NPAS) (McNicholas et al., 1988; Sloan et al., 1990). This abstinence as measured by the NPAS score was more severe in diazepam- and halazepam-dependent than in nordiazepam-dependent dogs whereas the incidence of precipitated clonic seizures was greater in the diazepam- and nordiazepam-dependent than in the halazepam-dependent dogs. Pharmacokinetic studies showed that in the dog the major conversion of halazepam, like diazepam, was to nordiazepam and an oxazepam conjugate. Appreciable quantities of oxazepam, 3-OH halazepam and its conjugated metabolite were also identified in plasma. The NPAS score obtained in the halazepam-dependent dogs, however, was greater than the NPAS score obtained in nordiazepam-dependent dogs who had nordiazepam plasma levels over three times higher than those obtained in the halazepam-dependent dogs. Further, the precipitated abstinence observed in the halazepam-, diazepam- and nordiazepam-dependent dogs differed in qualitative as well as in quantitative aspects including marked differences in the time course of abstinence signs. These data argue that the different dependencies produced by halazepam, diazepam and nordiazepam are not due solely to either the parent compound or to a single metabolite but most likely to their combined effects.

Administration, Oral↗

PubMed1991

The FDG/PET methodology for early detection of disease onset: a statistical model.

The development of appropriate statistical methodologies for neuroimaging studies is dependent upon the research question of interest. Often studies are analyzed with techniques that may not be appropriate for the research question but are accepted owing to convention, familiarity, or apparent statistical sophistication. Neuroimaging data are particularly complex owing to (a) the high number of potential dependent variables (i.e., regions of interest) coupled with the practical limitations on sample size; (b) the known physical properties of scanners (e.g., resolution) interacting with the intricate and variable structure of the human brain; and (c) mathematical properties introduced into the data by the physiological model for quantification. In this article, a statistical model will be discussed for addressing a particular problem in clinical studies. Given that there is a characteristic abnormality in regional glucose metabolism in a specific disease, can a probabilistic statement be made with confidence regarding the likelihood of an individual scan being similar to those from the disease group or normal subjects? The model capitalizes on known statistical aspects of normal regional glucose metabolism. To illustrate the model, data will be presented on normal subjects, patients with confirmed Huntington's disease, and subjects at risk for the disease. Reliability and clinical validity of the model will be discussed.

Adult↗

PubMed1991

The nigrostriatal dopaminergic pathway in Wilson's disease studied with positron emission tomography.

Movement disorders, including Parkinsonism, are prominent features of neurological Wilson's disease (WD). This suggests there may be dysfunction of the nigrostriatal dopaminergic pathway. To explore this possibility, five patients were studied using positron emission tomography (PET) with 18F-6-fluorodopa (6FD), and magnetic resonance imaging (MRI). We calculated striatal 6FD uptake rate constants by a graphical method and compared the results with those of 18 normal subjects. It was found that four patients with symptoms all had abnormally low 6FD uptake, and the one asymptomatic patient had normal uptake. PET evidence for nigrostriatal dopaminergic dysfunction was present even after many years of penicillamine treatment. It is concluded that the nigrostriatal dopaminergic pathway is involved in neurological WD.

Adult↗

PubMed1991

Complications of general anesthesia for Nd:YAG laser resection of endobronchial tumors.

We studied the incidence and mechanisms of cardiovascular complications and postoperative respiratory insufficiency associated with GA and Nd:YAG laser endobronchial tumor resection. The records of 73 patients undergoing 87 procedures were reviewed. Preoperative status, anesthetic methods and perioperative complications were analyzed by multiple regression to determine predictors of outcome. Twenty-three percent of patients had greater than 90 percent mainstem bronchus obstruction. Longer serum elimination half-life of relaxant drug was significantly correlated with longer duration of mechanical ventilation after neuromuscular blockade reversal. Cardiovascular complications were noted in 24 procedures and often required therapeutic intervention. Variables predicting cardiovascular complications included longer duration of GA and increasing age. Perioperative respiratory and cardiovascular complications are common after GA for Nd: YAG laser resection. Short-acting neuromuscular relaxants, careful assessment prior to postoperative extubation, limiting duration of GA and cardiovascular monitoring are recommended when implementing GA for Nd: YAG laser resection of endobronchial tumors.

Adenocarcinoma↗

PubMed1991

Closure of a bronchopleural fistula with bronchoscopic instillation of tetracycline.

Persistent bronchopleural fistulas (BPF) due to infection, trauma, or thoracic surgical procedures are often difficult to manage. We report a patient with fulminant Staphylococcus aureus pneumonia complicated by chronic BPF formation which prevented weaning from mechanical ventilation due to severe air leak. Fistula closure was obtained by instillation of tetracycline into the fistula via a fiberoptic bronchoscope using a balloon catheter and blood clot occlusion technique. This closed the BPF and allowed successful weaning from mechanical ventilation.

Adolescent↗

PubMed1990

[Clinical experiences with early colonoscopic decompression in acute pseudo-obstruction of the colon].

The prognosis of an acute colonic pseudoobstruction has improved significantly since the introduction of colonoscopic decompression. Our experience confirms this technique as a safe and effective therapy even for critically ill patients. In most of our cases several endoscopic decompressions were necessary before a lasting improvement of the clinical symptoms could be achieved. The additional use of new procinetic substances and the endoscopic placement of thick decompression tubes may reduce the number of endoscopic procedures necessary for each patient.

Acute Disease↗

PubMed1990

Positron emission tomographic scanning demonstrates a presynaptic dopaminergic lesion in Lytico-Bodig. The amyotrophic lateral sclerosis-parkinsonism-dementia complex of Guam.

We performed positron emission tomography using 18F-6-fluorodopa on four Guamanians with an amyotrophic lateral sclerosis syndrome, eight Guamanians with parkinsonism, and seven clinically normal Guamanians; the results were compared with those of nine Vancouver control subjects. The Guamanian subjects had all been exposed to similar Chamorro lifestyles. The scans were analyzed using a graphic method that calculates a constant for whole striatal 18F-6-fluorodopa uptake. The parkinsonian subjects all had significantly reduced striatal 18F-6-fluorodopa uptake. The group with amyotrophic lateral sclerosis had significantly reduced uptake that was intermediate between that of the control group and the parkinsonian group. Two Guamanian normal subjects had reduced striatal 18F-6-fluorodopa uptake. The nigrostriatal dopaminergic lesion in Guamanian parkinsonism is similar to that found in idiopathic parkinsonism. The nigrostriatal lesions in the subjects with amyotrophic lateral sclerosis and the Guamanian normal subjects are examples of subclinical neuronal damage demonstrable in living subjects with positron emission tomography.

Adult↗

PubMed1990

Positron emission tomography in Shy-Drager syndrome.

We studied the nigrostriatal dopaminergic pathway in 3 patients with Shy-Drager syndrome, by using positron emission tomography and [18F]6-fluoro-1-dopa to determine whether their parkinsonism correlated with impaired functional integrity of the presynaptic nigrostriatal pathway. One patient had short duration of disease, mild parkinsonism, and a normal positron emission tomographic scan, suggesting pathological changes functionally distal to the nigrostriatal pathway. Two patients with longer duration of disease had more severe parkinsonism and reduced [18F]6-fluoro-1-dopa uptake, suggesting impaired nigrostriatal dopaminergic function with progression of Shy-Drager syndrome.

Aged↗