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Biomedical subjects

R Marsh

Publications and source records attributed to R Marsh.

At least 37 records · Page 2Linked to original sources

Myelin glycoprotein P0 is expressed at early stages of chicken and rat embryogenesis.

Although previous studies suggest that P0 is expressed only in myelinating Schwann cells, monoclonal antibody 1E8 reacts with P0, yet also stains early Schwann cell precursors and non-myelinating Schwann cells (Bhattacharyya et al.: Neuron 7:831-844, 1991). We therefore characterized the 1E8 epitope and analyzed P0 mRNA expression during development. Immunoblot analyses of P0 fusion proteins and of deglycosylated P0 indicated that the 1E8 epitope is polypeptide. Northern blot and polymerase chain reaction (PCR) analyses revealed that P0 is encoded by a single mRNA that is expressed in chicken embryos as early as E4 and in rat embryos as early as E14. These data indicate that the antigen recognized by 1E8 in early chicken embryos is P0 and that, during development of both chickens and rats, P0 mRNA is expressed long before myelination.

Animals↗

Pharmacokinetic and pharmacodynamic responses to caffeine in poor and normal sleepers.

Pharmacokinetic and pharmacodynamic responses to caffeine (2.5 mg/kg) were compared between ten healthy self-rated poor sleepers and ten normal sleepers. Sleep pattern assessed by the Pittsburgh Sleep Quality Index (PSQI). There was no significant difference in mean estimated daily caffeine consumption between the groups. The poor sleepers had significantly higher scores for neuroticism on the Eysenck Personality Questionnaire (EPQ) and anxiety on the Hospital Anxiety Depression (HAD) scale, compared with normal sleepers. Caffeine pharmacokinetics were assessed by measurement of saliva caffeine concentrations. Poor sleepers showed significantly greater variability in caffeine Cmax, clearance had half-life, compared to normal sleepers. Pharmacodynamic measures included heart rate, blood pressure, visual analogue scales for concentration, vigilance and relaxation, psychomotor performance [Digit Symbol Substitution Test (DSST) and tapping rate (TR)] and EEG activity [Contingent negative variation (CNV), auditory evoked potential and power spectral analysis]. Prior to caffeine administration, poor sleepers compared to normal sleepers had faster heart rates, lower ratings for concentration and relaxation, poorer performance on the DSST, greater CNV magnitude, faster peak alpha frequency and lower delta, theta and beta power. These differences persisted after caffeine ingestion and overall differences between the groups on these measures were significant (P < 0.01-.001). Post-dose, but not pre-dose, scores for vigilance and TR were significantly lower overall in poor compared with normal sleepers. Despite the baseline differences between poor and normal sleepers, the changes following caffeine administration were similar in direction and magnitude in both groups.

Adult↗

Downstaging of esophageal cancer after preoperative radiation and chemotherapy.

OBJECTIVE: This retrospective, nonrandomized review evaluates 125 patients with esophageal carcinoma (adenocarcinoma and squamous cell) who underwent either surgery only or preoperative chemotherapy and/or radiation therapy followed by surgery. Major end points were survival and postchemoradiation downstaging. METHODS: Forty-four patients underwent radiation therapy of 4500 cGy over 5 weeks. Fluorouracil and cisplatin were administered on the first and fifth week of radiotherapy. Ninety-eight patients underwent "potentially curative" resections-transhiatal esophagectomy (70), Lewis esophagogastrectomy (25), and left esophagogastrectomy (3). All patients with preoperative adjuvant therapy underwent endoscopy and biopsy before surgery. RESULTS: There were no differences in overall mortality (5%) or surgical complications in either group. Fourteen of 44 patients (32%) downstaged to complete pathologic response, with 5-year survival of 57%. Fifteen of 44 patients (34%) downstaged to microscopic residual tumor, with 1- and 3-year survival of 77% and 31%, respectively. Twenty-eight of 29 patients in the two downstaged groups were lymph node negative. Overall, 5-year survival in the adjuvant therapy plus surgery group versus surgery only was 36% and 11% (p = 0.04). Five-year survival in lymph node-negative adjuvant therapy and surgery patients was 49% (p = 0.005). Positive nodes in the surgery only group was 48% versus 23% in the adjuvant therapy and surgery group (p = 0.02). CONCLUSION: Although retrospective and nonrandomized, these results suggest that preoperative chemoradiation results in significant clinical and pathologic downstaging, increases survival, and may sterilize local and regional lymph nodes, accounting for both downstaging and survival statistics.

Adenocarcinoma↗

Vascular network changes in the retina with age and hypertension.

OBJECTIVE: To compare retinal arterial bifurcation geometry in normotensive and hypertensive subjects. DESIGN: A retrospective observational study. METHODS: Fluorescein angiograms of normotensive (n = 13) and hypertensive (n = 12) subjects aged 30-80 years with uni-ocular retinal pathology were compared. Quantification of diameters of the parent, larger daughter and smaller daughter vessels (d0, d1 and d2, respectively) and of bifurcation angles (the angle between the two daughter arterioles, omega) of arteriolar bifurcations was performed from digitized retinal angiograms of the uninvolved eye. The relative diameters of parent and daughter vessels at bifurcations were summarized by junction exponents (x) such that d1x + d2x = d0x. RESULTS: Junction exponents were similar for normotensives and hypertensives (means +/- SEM, 2.65 +/- 0.18 and 2.48 +/- 0.17), but analysis of covariance showed a parallel decrease in x in the two groups with age. A positive association was found between x and arteriolar microvascular density. Bifurcation angles were more acute in hypertensives (74 +/- 3 degrees) than in normotensives (84 +/- 3 degrees) and declined with increasing age in both groups. CONCLUSIONS: The present findings indicate that ageing and possibly hypertension are associated with disadvantageous branching geometry in the human retinal vasculature, implying increased power costs of blood transport, uneven distribution of shear forces throughout the vascular tree and microvascular rarefaction. The present findings may have important implications for our understanding of the pathogenesis of vascular disease in ageing and hypertension and offer the prospect of a novel sensitive diagnostic approach to the cardiovascular system.

Adult↗

The effect of light on the vitamin B2 and the vitamin A content of cheese.

Edam type cheese was exposed to sunlight at ambient temperature and to fluorescent light at 5 degrees C. The loss of vitamin B2 (riboflavin) and vitamin A was monitored in both the surface and inner layers of the cheese and the results compared with control samples kept in the dark. The loss of riboflavin when exposed to sunlight was shown to be primarily a surface effect but losses of vitamin A were similar throughout the cheese. When exposed to fluorescent light at 5 degrees C and monitored at intervals for 10 days the loss of riboflavin was still greatest at the surface but a trend to lower values than the control was evident throughout the cheese. Vitamin A losses followed a different pattern in both sunlight and fluorescent light. There was a heavy initial loss throughout the cheese. Under fluorescent light this was followed by a period in which further loss was mainly in the surface layer. Vacuum packaging reduced the loss of riboflavin but had no effect on the loss of vitamin A.

Cheese↗

Amphotericin B delays both scrapie agent replication and PrP-res accumulation early in infection.

Amphotericin B delays the onset of clinical symptoms in hamsters infected with scrapie agent strain 263K. Here we show that accumulation of a scrapie-specific isoform of the prion protein (PrP-res) and agent replication were delayed early in amphotericin B-treated animals. By 8 weeks postinfection, only untreated animals exhibited clinical symptoms of scrapie infection whereas PrP-res levels and titers were similar in treated and untreated animals. This suggests that although PrP-res accumulation and agent replication are linked, they are not the sole factors required for the onset of clinical disease.

Amphotericin B↗

Results of a structured psychiatric interview to evaluate NASA astronaut candidates.

One hundred six astronaut applicants who had passed initial screening were evaluated for Axis I and Axis II DSM-III-R diagnoses using a structured psychiatric interview. Nine of 106 candidates (8.5%) met diagnostic criteria for six Axis I (including V-code), or Axis II disorders. The use of the NASA structured interview was effective in identifying past and present psychopathology in a group of highly motivated and healthy astronaut applicants. This was the first time that a structured interview had been used in such a setting for this purpose. The methodology described is applicable to any situation where the presence or history of psychopathology requires evaluation for job selection (e.g. pilot selection).

Aerospace Medicine↗

The efficacy of cefaclor vs amoxicillin on recovery after tonsillectomy in children.

Tonsillectomy and adenoidectomy continues to be one of the most commonly performed operations in the pediatric age group. The morbidity from tonsillectomy can be severe and includes throat and ear pain, fever, lethargy, and poor oral intake. A previous study at the Children's Hospital of Philadelphia (Pa) demonstrated the efficacy of amoxicillin therapy in minimizing some of these postoperative symptoms. However, some children continue to have a prolonged recovery even while receiving this antibiotic regimen. Because of these children and the high incidence of Staphylococcus found in tonsillar core tissue, a randomized, prospective study was undertaken at the Children's Hospital of Philadelphia to evaluate the efficacy of cefaclor vs amoxicillin in patients recovering from tonsillectomy. The patients received either ampicillin or cefazolin intravenously at the time of surgery and for 12 to 24 hours postoperatively. When oral intake was adequate, they received either amoxicillin or cefaclor orally for 7 additional postoperative days. Intraoperative cultures of the oropharynx and tonsillar tissue were obtained, as well as cultures of the tonsillar fossa 7 to 14 days postoperatively. The patients were evaluated for severity and duration of postoperative symptoms as well as complications. The results of this study showed no difference between the two groups of patients. We conclude that there is no justification for routine use of cefaclor over amoxicillin in the posttonsillectomy patient.

Amoxicillin↗

Treatment of cytomegalovirus retinitis with zidovudine and ganciclovir in patients with AIDS: outcome and toxicity.

Sixteen patients with the Acquired Immunodeficiency Syndrome (AIDS) and cytomegalovirus retinitis were treated with ganciclovir alone (9 patients) or ganciclovir and zidovudine (6 patients). The duration of effective treatment, that is the number of weeks during which there was no deterioration in visual symptoms or retinal appearance, was comparable in both groups. However, six of the seven patients receiving concurrent therapy had to cease treatment temporarily because of bone marrow toxicity compared with one of the nine patients treated with ganciclovir alone. It is concluded that continuous concurrent therapy with oral zidovudine and intravenous ganciclovir is not possible unless unlimited supportive therapy including blood transfusion, is available.

Acquired Immunodeficiency Syndrome↗

Insulin-like growth factor I stimulates proliferation, migration, and plasminogen activator release by human retinal pigment epithelial cells.

The migration of retinal pigment epithelial (RPE) cells from their normal anatomic position to a new position in the vitreous cavity is a critical feature of proliferative vitreous retinopathy. To determine if insulin-like growth factor I (IGF I), which is present in the vitreous fluid of diabetics, stimulates RPE cells, we examined the effects of IGF I on the proliferation, chemotaxis, and release of plasminogen activator by these cells. At the concentrations of IGF I tested, significant proliferation of RPE cells is seen. Significant chemotaxis of the RPE cells also is seen at all the concentrations of IGF I tested. The mean number of migrating cells per high-powered field in control studies was 43 +/- 13 (x +/- SEM), and for IGF I at 2.5 ng and 50 ng/ml the mean numbers of migrating cells were 96 +/- 17 and 483 +/- 62, respectively (P less than 0.001 for each comparison). The IGF I response was noted to be dose-dependent. The chemotactic response noted at 50 ng/ml of IGF I was greater than the positive chemotactic control of 10% fetal calf serum. Addition of alpha IR-3, an IGF I receptor antibody, eliminated the IGF I chemotactic response. The effect of IGF I on the secretion of plasminogen activators was assessed using an immunological assay for tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI). Media conditioned by RPE cells have measureable levels of PAI and t-PA antigen. IGF I supplementation resulted in an increase of t-PA secretion and PAI secretion over basal levels. These studies support a role for IGF I in modulating RPE cell function.

Antibodies, Monoclonal↗

Transcutaneous electrical nerve stimulation produces variable changes in somatosensory evoked potentials, sensory perception and pain threshold: clinical implications for pain relief.

Transcutaneous electrical nerve stimulation decreased early and late somatosensory evoked potential amplitudes and stimulus intensity ratings, and elevated sensory detection threshold, in normal subjects. Effects on pain threshold depended on pre-treatment threshold. These findings are relevant to treatment of clinical pain by transcutaneous electrical nerve stimulation.

Adult↗

ECG lead checker.

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Electrocardiography↗

Conversion of atrial fibrillation to sinus rhythm by acute intravenous procainamide infusion.

We evaluated the efficacy of an intravenous infusion of procainamide in 26 consecutive candidates for cardioversion of atrial fibrillation. Procainamide was administered at a rate of 15 to 20 mg/min up to a maximum of 1000 mg. The treatment was considered effective only if cardioversion occurred during the procainamide infusion. Conversion to sinus rhythm occurred in 15 patients. Converters had a significantly shorter mean duration of atrial fibrillation (6 +/- 7 days, mean +/- S.D.) compared to nonconverters (79 +/- 88 days) (p less than 0.01). The mean left atrial size of converters (4.3 +/- 0.6 cm) did not differ significantly from that of nonconverters (4.7 +/- 0.9 cm). The dose of procainamide required for cardioversion ranged from 3.6 to 16.4 mg/kg. Two patients developed nonsustained ventricular tachycardia, and there was one episode of bifascicular block during the infusion. Intravenous procainamide is an effective form of therapy for conversion of atrial fibrillation of new onset.

Adult↗

The effects of deep barbiturate coma on multimodality evoked potentials.

The authors report their investigation of the effects of high-dose barbiturates on the multimodality evoked response in 9 cats. After baseline evoked responses were obtained, boluses of pentobarbital were infused intravenously at regular intervals, amounting to cumulative total doses of 9, 18, 27, 45, 63, 123, and 183 mg/kg at respective infusions. This resulted in gradually increasing serum pentobarbital levels, reaching therapeutic coma levels (4 to 5 mg/dl) after the fifth infusion. At this point, the electroencephalogram was flat, and pressor agents were required to maintain cardiovascular stability. Evoked responses were obtained 15 minutes after each infusion. Brain-stem auditory evoked response (BAER) showed little change in wave latencies at therapeutic coma levels of pentobarbital. Further barbiturates resulted in delay of the late components of this response. In the somatosensory evoked responses (SER), early brain-stem components were relatively unaffected by therapeutic coma levels. Late brain-stem components and the initial cortical response showed progressive latency increase. Late cortical (association cortex) waves were abolished at relatively low doses. The central conduction time was relatively unaffected. The late waves of the visual evoked responses (VER) were abolished with low-dose barbiturates (9 mg/kg). A single positive-negative complex persisted despite massive infusions. It is concluded that evoked responses may prove useful in monitoring patients in deep barbiturate coma, but barbiturate effects must be kept in mind.

Animals↗