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Biomedical subjects

M McGuire

Publications and source records attributed to M McGuire.

At least 19 recordsLinked to original sources

Characterization of the percepts evoked by discontinuous motion over the perioral skin.

The capacity of human subjects to process information about discontinuous and continuous movement was evaluated. Constant-velocity brushing stimuli were delivered through aperture plates that rested lightly upon the mandibular skin. Each plate consisted of either two spatially separated, slit-like openings or a single continuous, longer opening. It was discovered that percepts of smooth apparent motion were achieved with the split apertures (i.e., from discontinuous movement) for only limited ranges of stimulus velocity. Moreover, the optimal velocity supporting smooth apparent motion increased with the separation between the slit-like openings. In a second series of experiments, subjects' ability to discriminate opposing directions of discontinuous and continuous movement was evaluated. It was found that subjects could derive directional information from percepts elicited by discontinuous movement. However, the capacity to discriminate opposing directions of continuous movement cannot be explained solely in terms of the ability to process information about the change in position of a stimulus from its onset to its offset.

Discrimination Learning

An analysis of the diagnostic accuracy of endoscopic biopsy and cytology in the detection of oesophageal malignancy.

The role of combined cytohistological examination in the differentiation of benign from malignant oesophageal mucosal lesions was studied in 331 patients. Malignancy was confirmed by specimen histopathology in 58 patients. Both endoscopic biopsy and cytology were positive in 41 (71%) patients. Endoscopic biopsy alone suggested malignancy in 10 cases (17%) while cytology was positive after negative biopsy in seven (12%). Cytology yielded four false positive and 10 false negative results giving a sensitivity level of 81%, a specificity of 98% and a positive predictive value for oesophageal malignancy of 92%. Histology on the other hand yielded one false positive and seven false negative results providing a sensitivity of 87%, a specificity of 99% and a positive predictive value of 96%. No patients were left undiagnosed using both diagnostic modalities; cytology increased the diagnostic yield from 87% to 100%. Exfoliative cytology was most valuable in the diagnosis of tumours of the lower one-third of the oesophagus where seven of 31 malignancies (23%) were identified by this method alone (P less than 0.05). Neither the histological type of the tumour nor the morphological appearance was found significantly to affect the diagnostic yield (P greater than 0.05). We conclude that cytological examination should be standard practice in the investigation of oesophageal lesions.

Biopsy

Simulated paraphilias: a preliminary study of patients who imitate or exaggerate paraphilic symptoms and behaviors.

In a consecutive series of admissions to the Johns Hopkins Sexual Disorders Unit, 4 out of 20 patients appeared to have simulated paraphilic symptoms that further assessment indicated were either exaggerated or not present. The paper presents case histories of these 4 patients. A descriptive comparison is made between these patients and control groups of patients who admitted having paraphilic symptoms and a group of patients accused of having paraphilic symptoms but who denied them. Patients who simulated paraphilias tended to be self-referred (75%) and without current legal charges (100%). None of these patients was referred or sought treatment for pedophilia, in contrast to the other two patient groups, in which pedophilia accounted for 75% of the referrals. Several possible explanations for why patients might simulate paraphilias and implications for therapists who evaluate or treat sex offenders are discussed.

Adult

Urinary cytology in the detection of bladder carcinoma.

We have analysed the accuracy of cytological examination of voided urine in a population of 265 patients presenting with suspected bladder lesions. Bladder carcinoma was confirmed by tissue histopathology in 51 patients. Of these, 42 were identified correctly by urinary cytology examination. Overall 34 patients were labelled as frankly malignant on cytology, of whom 2 were negative on final histology. 13 patients had been designated as suspicious however with 3 benign on final histological diagnosis. These data give a sensitivity for diagnosis of bladder cancer by urinary cytology of 82%, a specificity of 97%, a positive predictive value of 94%, and a negative predictive value of 96%.

Adolescent

Corticotropin-releasing hormone inhibits maternal behavior and induces pup-killing.

Behavioral responses to stressors and the effects of stressors on maternal behavior change with mothering experience. Corticotropin-releasing hormone (CRH) is released by stressors and produces stress-like behavioral effects. We tested the effects of ICV infusion of ovine CRH (0.5-4 ug) on pup-directed behaviors in ovariectomized, ovarian steroid-treated virgin rats that were either naive to pups or that had three days of mothering experience. CRH inhibited maternal behavior in naive and experienced rats in a dose-related manner. The magnitude and duration of inhibition, especially at the 1 ug dose, were less in rats with mothering experience. Higher doses of CRH (1 - 4 ug) significantly increased pup-killing in rats that were naive to pups. In contrast, CRH produced no pup-killing in rats with mothering experience.

Animals

Effects of acetate dialysate on transforming growth factor beta 1, interleukin, and beta 2-microglobulin plasma levels.

To evaluate potential adverse effects of acetate use in hemodialysis (HD), we measured plasma interleukin (IL-1 alpha, IL-1 beta, IL-6), TNF alpha, TGF beta 1, and beta 2-microglobulin levels with ELISA assays in normal (N = 9), CRF (N = 6), CAPD (N = 7) and HD (N = 8) subjects and compared the effects of acetate (Ac) and acetate-free (Ac-free) dialysate. TGF beta 1 was the only cytokine consistently detected. Compared to normals (median 57, range 53 to 68 pg/ml, one undetected; N = 8), TGF beta 1 was higher in the CRF (75, 70 to 97 pg/ml, one undetected) and CAPD (75.5, 66 to 116 pg/ml, N = 6) groups (P less than 0.05), and was somewhat higher in the HD (68, 52 to 88 pg/ml) group (P less than 0.10). Acutely, TGF beta 1 pre-HD (70, 63 to 88 pg/ml) increased above normals post AcHD [79.5, 65 to 140 pg/ml uncorrected for ultrafiltration (UF)] and was higher after AcHD versus Ac-free HD both uncorrected (79.5, 65 to 140 pg/ml vs. 70, 52 to 86 pg/ml) and corrected for UF (68, 51 to 115 pg/ml vs. 57, 43 to 69 pg/ml; P less than 0.05). beta 2-microglobulin was not different after AcHD (81.2 +/- 8.0 mg/ml) versus Ac-free HD (72.5 +/- 6.9 mg/ml). Significantly lower serum inorganic phosphorus was also found four hours post-AcHD compared to four hours post-Ac-free HD (0.87 mmol +/- 0.10 SEM vs. 1.05 mmol +/- 0.07 SEM; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates

Electric field stimulation of human osteosarcoma-derived cells: a dose-response study.

In vitro electrical stimulation of human osteosarcoma-derived cells resulted in increased cell adherence and current directed cell migration. We have developed an electrical exposure system in which two steel electrodes imbedded in media-based agar, poured in a standard culture dish, are used to apply electric field signals to cells in culture without ion contamination from the electrodes. The cells were exposed to a 100 Hz pulsed DC electric signal at peak field strengths of 1, 10, 100, and 625 mV/cm in the culture media. The data showed no change in cell adherence at 1 and 10 mV/cm, an increase in adherence at 100 mV/cm, and a decrease in both adherence and cell proliferation at 625 mV/cm. Electric field stimulation in vivo has been found useful in accelerating the healing of fractures and non-unions, and the repair of surgical and cancer-related skeletal defects.

Biophysical Phenomena

The role of aspiration cytologic examination in the diagnosis of carcinoma of the breast.

A study of 2,000 patients who had undergone fine needle aspiration of a solid lump of the breast was conducted to determine the accuracy of this technique. During the period 1982 to 1989, all patients with a solid mammary mass, presenting to a specialized breast unit were initially investigated by fine needle aspiration cytologic examination (FNAC). To date, we present data on 2,000 consecutive aspirations with matching histologic diagnosis on the excised pathologic specimens. In particular, the relationship between tumor histologic factors and the accuracy of cytologic diagnosis was examined. The sensitivity of FNAC in the diagnosis of a malignant growth was 84 per cent; this represents first aspiration results only. The specificity was more than 99 per cent. The rate of acellular or unsatisfactory aspirations was 12 per cent. We had a positive predictive rate for diagnosis in carcinoma of the breast of almost 95 per cent. The diagnosis of lobular and in situ patterns of disease was questioned, with three of three in situ lesions and ten of 23 lobular lesions missed by FNAC. We do not recommend that FNAC replace excision biopsy and frozen section in the diagnosis of carcinoma of the breast.

Biopsy, Needle

Specific identification of fibrin(ogen) degradation products in plasma and serum using blotting and peroxidase labeled antiserum.

We describe a method for identifying fibrinogen and fibrin split products using electrophoresis on agarose gel with sodium dodecyl sulfate (SDS) followed by blotting in nitrocellulose paper. Detection of these derivatives after blotting is accomplished with peroxidase-conjugated rather than by isotopically labeled antibodies. This technique can detect diverse fibrinogen derivatives produced in vivo or in vitro by the combined action of thrombin, plasmin, and factor XIII. This methodology is applicable to plasma, serum, and other body fluids including urine and ascitic fluid. This sensitive and specific assay, distinguishing the products of cross-linked fibrin from those of fibrinogen and detecting fibrin polymers in plasma, can be achieved without the use of radioactivity.

Blood

ECG evidence of limited myocardial infarction following coronary occlusion treated by early intravenous rt-PA infusion.

Serial 12-lead surface electrocardiograms (ECGs) were analysed in 110 patients with first evolving myocardial infarction entered in a double-blind placebo-controlled trial of intravenous rt-PA within 2.5 h (mean 1.9 +/- 0.5 (SD)) of pain onset. ECG analysis was performed by two 'blinded' analysts. QRS scoring (by the modified Selvester method) was used as an index of myocardial necrosis. Patient results were analysed according to infarct location. There was no difference between the two treatment groups in ST-segment elevation or QRS score at entry or up to 24 h after symptom onset. However from 24 h, QRS score was lower in patients with anterior infarction given rt-PA than in those given placebo: 5.4 +/- 2.8 vs 7.7 +/- 4.1 (P = 0.02) at 48 h; 4.7 +/- 3.2 vs 8.0 +/- 4.0 (P = 0.01) at 4-10 days; and 4.6 +/- 3.9 vs 7.5 +/- 3.9 (P = 0.01) at 21 days. For patients with inferior infarction, rt-PA treatment also resulted in a lower QRS score although this was not significantly different from the score of the placebo group (P = 0.07). Comparison of QRS scores with ejection fraction measured from the contrast ventriculogram taken at 21 days showed a moderate correlation (r = 0.46) in patients with anterior infarction but a poor correlation in patients with inferior infarction. These ECG results indicate that in evolving anterior myocardial infarction, there is limitation of infarct size from early rt-PA infusion.

Double-Blind Method

Plasma tumor necrosis factor alpha predicts decreased long-term survival in severe alcoholic hepatitis.

Plasma tumor necrosis factor alpha (TNF alpha), interleukin 1 alpha (IL-1 alpha), and interleukin 1 beta (IL-1 beta) were measured in plasma samples obtained from 23 patients with severe alcoholic hepatitis on admission and after 30 days of hospitalization. Over a 2-year follow-up period, 14 patients died at a mean time of 8 months following discharge. The presence of elevated plasma TNF alpha either at admission or discharge from the hospital was associated with death in 82% (14/17) of patients. By contrast absence of elevated plasma TNF alpha was associated with survival in 100% (6/6). The difference in survival with and without detectable plasma TNF alpha was significant at p = 0.0022. Plasma TNF alpha was not elevated in alcoholic patients without clinically apparent liver disease, with alcoholic cirrhosis, or in nonalcoholic healthy controls. Plasma IL-1 alpha was also significantly increased in alcoholic hepatitis whereas IL-1 beta was not. Neither IL-1 alpha nor beta was correlated with outcome in the alcoholic hepatitis group. It is concluded that the presence of elevated plasma TNF alpha is a significant predictor of decreased long-term survival in patients with severe alcoholic hepatitis.

Adult

Distal oesophageal ph monitoring for gastro-oesophageal reflux.

We investigated eight hour distal intra-oesophageal ph testing to see if this could replace the traditional 24 hour test period without significant loss of sensitivity in the diagnosis of gastro-oesophageal reflux (GOR) disease in symptomatic refluxers. Thirty-four patients were tested, all of whom had classical De Meester symptoms of GOR. All patients were admitted to hospital and commenced on 24 hour ambulant ph monitoring of the distal oesophagus. This was followed by a period of eight hour testing. The following variables were determined: (i) total reflux time, (ii) number of reflux episodes (total, upright and supine), (iii) longest episode of reflux, (iv) percent of time that ph was below four (total, upright and supine). All patients underwent endoscopic examination of the oesophagus subsequently. Twenty four hour monitoring resulted in a positive diagnosis of GOR in 26 of 34 patients, giving an overall sensitivity of 75%. Eight hour testing was positive in 23 patients (sensitivity of 68%, not significantly different). The best correlations were obtained when comparing total reflux episodes (r = 0.75, p less than 0.001), and the percent time ph less than 4 (total) (r = 0.69, p less than 0.001). Nineteen patients had evidence of oesophagitis on endoscopy, and in all such patients both eight and 24 hour testing were positive. We conclude therefore, that eight hour ph monitoring can be reliably used in the diagnosis of pathological GOR in patients symptomatic for acid reflux.

Esophagitis

Combined endoscopic cytology and biopsies in the diagnosis of duodenal malignancy.

The value of combined cytohistochemical examination in the diagnosis of malignant duodenal lesions was assessed in 78 patients with suspicious duodenal lesions seen at endoscopy. Cytological smears were taken using the direct-vision brushing technique and all were processed by the same experienced cytologist. Duodenal malignancy was confirmed histologically in four patients. Endoscopic biopsy was positive for malignancy in three of the patients and cytology was suspicious of malignant change in two patients and positive for malignant change in one patient. Cytology alone confirmed the diagnosis of malignancy in one patient. The cumulative diagnostic yield using both biopsy and cytology was 100%.

Biopsy

Involvement of the 'leucine zipper' region in the oligomerization and transforming activity of human c-myc protein.

c-Myc plays a part in the regulation of important cellular processes such as growth, differentiation and neoplastic transformation. Although c-myc gene structure and expression are well characterized, the function and biochemical properties of the protein are less well understood. Human c-myc is a 439-amino acid phosphoprotein which binds DNA in vitro and belongs to a discrete subset of nuclear proteins. Using the human c-myc mutants generated by linker-insertion and deletion mutagenesis, we have defined regions of the protein that are important for its transforming activities and its nuclear localization. Here, we show that human c-myc exists as an oligomer in vitro and use mutant proteins to localize the oligomerization domain to a carboxyl-terminal peptide containing the 'leucine zipper' motif. The 'leucine zipper' describes a structure found in a number of DNA-binding proteins that contains leucines occurring at intervals of every seventh amino acid in a region predicted to be alpha-helical. The 'leucine zipper' might mediate dimerization by intermolecular interdigitation of the leucine side-chains. We show that a c-myc mutant, which is inactive but can oligomerize, dominantly inhibits the cotransforming activity with wild-type c-myc of rat embryo cells, whereas inactive mutants which cannot oligomerize properly because of deletions in the oligomerization domain are recessive.

Animals

Spontaneous and induced chromosome breakage in chorionic villus samples: a cytogenetic approach to first trimester prenatal diagnosis of ataxia telangiectasia syndrome.

Patients with ataxia telangiectasia (AT) syndrome exhibit a high level of spontaneous chromosome aberrations, with hypersensitivity to gamma radiation and radiomimetic chemicals at the chromosomal and cellular level. Previously pregnancies at risk for AT have been screened solely by analysis of amniotic fluid samples. In this report we describe a cytogenetic approach to the prenatal diagnosis of AT using chorionic villus sampling (CVS). Levels of spontaneous and induced (gamma radiation and bleomycin) chromosome breakage were established in direct, semidirect, and culture preparations of CVS samples from normal pregnancies. The methods developed were then successfully applied to the screening of a pregnancy at risk for AT. Semidirect preparations showed normal levels of chromosome breakage, and this result was further confirmed in chorion, amniotic fluid, and lymphocyte cultures. In chorion villus samples, gamma radiation is probably the easiest and most reliable way of discriminating between unaffected fetuses and those with AT.

Adult

Natural history of late potentials in the first ten days after acute myocardial infarction and relation to early ventricular arrhythmias.

Serial signal-averaged electrocardiograms (ECGs) were performed every 48 hours in 50 patients admitted to the coronary care unit with acute myocardial infarction. The prevalence of late potentials was 32% at presentation (mean time to recording 12.4 +/- 6.6 hours after onset of chest pain) and increased progressively throughout the hospital stay. New late potentials were recorded in patients with no prior acute myocardial infarction as early as 3 hours after the onset of chest pain and as late as 8 days. Late potentials appeared transiently in only 3 patients. The detection of late potentials in the initial signal-averaged ECG identified patients with clinically significant early ventricular arrhythmias with a sensitivity of 80% and specificity of 72%. The predictive accuracy was 38% for a positive test and 94% for a negative test. Patients with early ventricular arrhythmias had significantly lower voltage in the terminal 40 ms of the filtered QRS complex (16 +/- 8 vs 32 +/- 19 microV, p less than 0.01) than those without arrhythmias. The signal-averaged ECG may be useful in identifying patients at high risk of developing clinically significant early ventricular arrhythmias after acute myocardial infarction.

Aged