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Biomedical subjects

D Benson

Publications and source records attributed to D Benson.

At least 19 recordsLinked to original sources

Hypokalemia, metabolic alkalosis, and hypertension: Cushing's syndrome in a patient with metastatic prostate adenocarcinoma.

Ectopic adrenocorticotropic hormone (ACTH) and/or corticotropin-releasing hormone (CRH) are associated with a growing list of tumors. We report a 69-year-old white man with a history of high-grade prostate carcinoma and widely metastatic adenocarcinoma who presented with metabolic alkalosis, hypokalemia, and hypertension secondary to ectopic ACTH and CRH secretion. Laboratory values were consistent with hypokalemia and metabolic alkalosis. Markedly elevated serum cortisol (135 microg/dL), ACTH (1,387 pg/dL), CRH (69 pg/dL), and urine free cortisol (16,276 microg/24 h) levels were found. Chest computed tomographic (CT) scan showed small noncalcified parenchymal densities; however, bronchoscopy and bronchoalveolar lavage washings were unremarkable for a neoplastic process. Abdominal CT scan and magnetic resonance imaging showed multiple small liver lesions and multiple thoracic and lumbar intensities consistent with diffuse metastatic disease. Histological analysis of a biopsy specimen from the thoracic spine showed an undifferentiated adenocarcinoma consistent with a prostate primary tumor. The severe metabolic alkalosis secondary to glucocorticoid-induced excessive mineralocorticoid activity was treated with potassium supplements, spironolactone, and ketoconazole. In this case report, we describe an unusual tumor associated with ectopic ACTH and CRH production and the pharmacodynamic relationship of plasma cortisol levels and urinary cortisol excretion with ketoconazole treatment.

ACTH Syndrome, Ectopic↗

CNS voltage-dependent Na(+) channel expression and distribution in an undifferentiated and differentiated CNS cell line.

Upon serum removal, CAD-R1 cells undergo neurite outgrowth and an increase in voltage-dependent Na(+) current (VDNaC) density without changing their activation and inactivation properties. Insulin and endothelial cell growth supplement inhibited the increase in VDNaC density but not the neurite outgrowth. RI, RII, RIII Na(+) channel proteins were expressed in CAD-R1 cells. These proteins exhibited both similar and different distribution and clustering patterns which suggested the channel's structural differences play a role in channel distribution.

Cell Culture Techniques↗

Chick ciliary ganglion neurons contain transcripts coding for acetylcholine receptor-associated protein at synapses (rapsyn).

A peripheral membrane protein of approximately 43 kDa (rapsyn) clusters muscle nicotinic acetylcholine receptors (AChRs), but molecules relevant to clustering neuronal AChRs have not been identified. Here, we have detected rapsyn transcripts in the chick nervous system, localized rapsyn mRNA in ciliary ganglion (CG) neurons, which are known to cluster AChRs, and identified three rapsyn cDNAs derived from the ganglion. Our initial Northern blots, performed using a mouse probe, revealed rapsyn-like transcripts in chick muscle and brain. To develop species-specific probes, we prepared a chick rapsyn cDNA construct, Ch43K.1, that encodes a protein having extensive homology to mouse rapsyn. Using primers designed to anneal near the 5' and 3' boundaries of Ch43K.1, three prominent cDNAs were amplified from chick muscle templates by reverse transcriptase based-PCR. Products of similar size were also amplified using cDNA prepared from neuronal tissues expected to contain clustered AChRs (CG and brain), whereas none were detected using templates from tissues not displaying clustered AChRs (sensory ganglia and liver). In situ hybridization confirmed that rapsyn mRNA is expressed both in chick muscle fibers and in CG neurons. Sequencing the three cDNAs amplified from CG templates revealed the largest to be Ch43K.1, whereas the smaller two may represent splice variants. These findings suggest that multiple rapsyn-like molecules are involved in clustering the distinct AChRs expressed by muscle fibers and neurons.

Amino Acid Sequence↗

Management of Jehovah's Witness patients for scoliosis surgery: the use of platelet and plasmapheresis.

Four patients whose religious beliefs prohibited accepting blood during surgery for scoliosis were anesthetized and managed successfully using plateletpheresis and plasmapheresis. Blood losses were replaced with crystalloid and hetastarch solutions. In addition, a moderate hypotensive technique was used to minimize surgical blood loss. Postoperatively, the patients received iron therapy and/or erythropoietin. Three of these patients had an uncomplicated postoperative course, however, the fourth patient had some postoperative bleeding with initial hemodynamic instability. We believe that patients who refuse to receive blood transfusion during surgery because of religious beliefs or health issues can be managed safely using other alternatives and techniques such as plateletpheresis and plasmapheresis, which conserve and minimize blood loss. Each case should be assessed on an individual basis.

Adolescent↗

Peripheral hypertension and alterations in pulmonary vascular regulation.

We have recently reported in normal isolated-perfused rat lungs that low basal tone appears to be regulated by nitric oxide (NO)-dependent and -independent mechanisms of soluble guanylate cyclase activation. In this study, we examined the role of NO in the regulation of pulmonary artery (PA) tone from rats with renin-dependent hypertension. Rats were made hypertensive by ligating the abdominal aorta above the left and below the right renal artery (aortic coarctation, AC). Mean arterial pressure significantly increased from 119 +/- 8.4 mmHg in control animals to 156 +/- 15 mmHg 7-14 days after AC surgery. PA pressures, however, remained unchanged (8.5 +/- 3.4 mmHg in control animals vs. 11 +/- 3.3 mmHg in AC animals). Hypoxic contractions in U-46619 precontracted isolated small PA (160-260 microns diameter) were significantly increased from 51 +/- 13 mg in the control group to 142 +/- 38 mg (P < or = 0.05) in AC animals. Nitro-L-arginine (NLA; 100 microM) contractions were also enhanced in the AC animal. The enhanced NLA response may correlate with an increase in endothelial cell NO synthase (NOS) as detected by Western blotting (132 +/- 28% of control; P < 0.05). These data suggest that, in this renin-dependent model of systemic hypertension, there is increased endothelial cell NOS activity that maintains low PA tone, preventing the lung from developing increased pressures.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

On the role of aging in carcinogenesis.

Correlation coefficients for age-standardized incidence rates between cancers of the stomach, colon, rectum and lung over place (worldwide) and time (in Connecticut) vary from positive to negative values, indicating that these cancers are not caused by common environmental agents. Correlation coefficients for age-incidence patterns (the variation in age-specific rates with age) between these cancers, on the other hand, are all highly positive for both sexes. We conclude that the carcinogenic determinants that vary with age are common to the cancers studied and to both sexes, and distinct from the carcinogenic determinants that vary with place and time. For the cancers studied, incidence rates are negligible until age 30, at which time they increase dramatically and continue to increase at least until age 75. The rate of increase, however, diminishes continuously with advancing age after 30. We suggest that the role of aging in cancer incidence is determined by two components, one responsible for the dramatic rate increase beginning near age 30 and one responsible for the gradual diminution in that rate increase. The former may correspond to the activation of quiescent cells with damaged DNA or to the deactivation of DNA surveillance or repair or to impaired apoptosis, while the latter may correspond to the loss of cell division potential.

Adult↗

Promoting use of a preferred histamine H2-receptor antagonist in managed care organizations.

A program to promote generic cimetidine as the preferred histamine H2-receptor antagonist (HRA) in the managed care organizations (MCOs) served by a pharmacy benefit management company is described. A pharmacy benefit management company conducted a literature review to substantiate the therapeutic equivalence of the HRAs and to set conservative criteria for identifying candidates for conversion to oral cimetidine therapy. During the third quarter of 1994, the prescriber for each patient identified was sent a document listing the patient's current HRA therapy, the date of his or her last prescription refill, and the name and telephone number of the dispensing pharmacy. A letter summarized the literature; outlined the criteria used to identify candidate patients; gave the current indications, dosages, and average wholesale prices of the HRAs; and asked the prescriber to switch the patient to generic cimetidine. HRA use in an MCO that participated in the program was compared with HRA use in a nonparticipating MCO for the second quarter of 1994 (the baseline period), the fourth quarter of 1994, and the first quarter of 1995. The nonparticipating MCO showed no change between baseline and 1995 in the proportion of HRA prescriptions accounted for by brand-name and generic cimetidine combined (14% for each period). The average acquisition cost per HRA prescription remained about $75 for each study quarter. In the participating MCO, the proportion of HRA prescriptions accounted for by brand-name plus generic cimetidine increased from 18% at baseline to 39% in the first quarter of 1995. The average acquisition cost per HRA prescription fell from $71 at baseline to $65 in the first quarter of 1995. A program to shift the use of brand-name HRAs to generic cimetidine in MCOs successfully altered prescribing patterns and reduced expenditures for these agents.

Cimetidine↗

Future directions for resuscitation research. I. Advanced airway control measures.

The efficacy of 'basic' airway control without equipment, using the combination of backward tilt of the head, forward displacement of the mandible, and separation of lips and teeth (i.e. the triple airway maneuver) has been well established. Direct mouth-to-mouth and mouth-to-nose ventilation must continue to be taught to the public. Further improvements are needed for pocket-size mouth-to-mouth barriers to combat infection risks. Dissemination of appropriate information on disease transmission is needed to ensure ventilation by health professionals, using exhaled air ventilation adjuncts and other devices. Much knowledge exists about the pathophysiology of airway obstruction. For patients in coma or anesthesia with airway obstruction, which resists basic airway control measures and standard tracheal intubation, available 'advanced' airway control measures should be mastered and improved. Preparedness for advanced airway control measures differs between elective management of the anticipated difficult airway for anesthesia and emergency airway control with unanticipated difficulties encountered during the ordinary sequential application of measures. Challenges include education research and development of new devices. For airway clearing, pharyngeal intubation, difficult tracheal intubation, cricothyrotomy, transtracheal jet ventilation and emergency use of oxygen - what could and should be taught, to whom, and how? Which new devices and training systems should be developed? The most important alternative to orotracheal or nasotracheal intubation recommended for the development of novel devices and teaching methods for health professionals, are cricothyrotomy (with wide enough airway to also enable spontaneous breathing of air), and translaryngeal or transtracheal oxygen jet ventilation. We recommend openness in communication and joint planning between anesthesiologists, emergency care providers, and appropriate educators, engineers and industries.

Cardiopulmonary Resuscitation↗

rK39: a cloned antigen of Leishmania chagasi that predicts active visceral leishmaniasis.

The diagnosis of visceral leishmaniasis (VL), a serious and often fatal parasitic disease caused by members of the Leishmania donovani complex, remains problematic. Current methods rely on clinical criteria, parasite identification in aspirate material, and serology. The latter methods use crude antigen preparations lacking in specificity. A previously described cloned antigen, rK39, of Leishmania specific for all members of the L. donovani complex (L. chagasi, L. donovani, L. infantum) was very useful in the serodiagnosis by ELISA of both human and canine VL. The present study demonstrated that rK39 seroreactivity correlated with active disease. The sera from early or self-healing infected subjects reacted with leishmanial lysate and were generally nonreactive with rK39. These data demonstrate the utility of rK39 in the serodiagnosis of VL and as an indicator of active disease.

Animals↗

GenBank.

The GenBank sequence database has undergone an expansion in data coverage, annotation content and the development of new services for the scientific community. In addition to nucleotide sequences, data from the major protein sequence and structural databases, and from U.S. and European patents is now included in an integrated system. MEDLINE abstracts from published articles describing the sequences provide an important new source of biological annotation for sequence entries. In addition to the continued support of existing services, new CD-ROM and network-based systems have been implemented for literature retrieval and sequence similarity searching. Major releases of GenBank are now more frequent and the data are distributed in several new forms for both end users and software developers.

Amino Acid Sequence↗

Red cell collection by apheresis technology.

To determine the feasibility of collecting 2 units (450 mL) of red cells per donation by apheresis technology, apheresis red cell collections were compared to whole-blood donations. Forty blood donors were equally divided between the two study arms on the basis of gender and iron supplementation (650 mg ferrous gluconate/day vs. no supplementation). During the 1-year study period, the apheresis participants donated 450 mL of red cells three times, and the whole-blood donors gave 225 mL of red cells (1 unit of blood) on six occasions. There were no reported side effects during the 102 whole-blood donations, whereas symptoms were noted in 83 percent of the 59 apheresis procedures. The most common symptoms were numbness and tingling, which were relieved by a decrease in the plasma-return rate or by the administration of oral calcium supplements. Seven donors dropped out or were deferred during the study. Two whole-blood donors left with medical problems unrelated to the study, one apheresis donor and one whole-blood donor dropped out of the study because of excessive fatigue, and three non-iron-supplemented whole-blood donors had unacceptably low hematocrit levels. By the end of the study, 70 percent of the apheresis donors considered the procedure acceptable, 15 percent were undecided, and 15 percent thought it was not acceptable. As measures of iron balance, the serum ferritin and the red cell zinc protoporphyrin:heme ratios were significantly more abnormal in the non-iron-supplemented donors than in the iron-supplemented donors. However, there were no differences in iron balance according to the donation method.

Adolescent↗

Extracoelomic approach to the spine.

A modified transthoracic approach to the thoracic vertebral column is described. In this method, the parietal pleura is detached from the chest wall and retracted with the visceral pleura and its contents. A direct approach to the vertebral bodies is thus achieved without transgression of the intrapleural space. The technique can be extended to include exposure of the thoracolumbar spinal column, utilising a thoracoabdominal approach with extrapleural and extraperitoneal dissection. Management of the costophrenic detachment is thus simplified. This approach has significant advantages for orthopaedic, vascular and neurosurgical procedures.

Adolescent↗

Patient experiences with multiband full dynamic range compression.

This investigation compared performance for 18 experienced hearing aid patients with a multiband full dynamic range compression hearing device and their previously worn linear or automatic gain control hearing aids. Performance was evaluated using a variety of clinical tests. These included functional gain and dynamic range measurements, speech recognition, and real ear measurements. Patients rated their performance with the multiband compression device and their previously worn aids on a rating scale pertaining to a variety of real life listening situations. Statistical analysis of data derived from test results shows significantly improved performance on all measures using the multiband compression aid over their conventional aids. Patients rated their performance higher with the compression instrument than with the conventional aids. Differences in performance on clinical tests and subjective patient responses appear to be related to the different signal processing schemes used in the two groups of devices.

Adolescent↗

Clenbuterol decreases catabolism and increases hypermetabolism in burned rats.

Following a 30% body surface area full-thickness open-flame burn, rats exhibited hypermetabolism, body weight loss, and muscle catabolism. Twenty-one days of treatment of one group of burned rats with the selective beta 2-adrenergic agonist, clenbuterol, increased resting energy expenditure and normalized body weight gain, muscle mass, and muscle protein content. Conversely, similar treatment of another group of burned rats with the long-acting beta-adrenergic antagonist, nadolol, reduced muscle mass, while having no effect on resting energy expenditure, body weight gain, or muscle protein content. These results demonstrate that hypermetabolism does not invariably result in loss of lean body mass and suggest that clenbuterol may be useful in preserving muscle mass and protein in catabolic diseases.

Amino Acids↗