Early amniocentesis: a cytogenetic evaluation.
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Biomedical subjects
Publications and source records attributed to J Smith.
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One thousand one hundred fifty-four cases of nonmelanoma skin cancer (NMSC) referred to the Consultative Skin Clinic at Peter MacCallum Cancer Institute (PMCI) (Melbourne, Australia) in 1980 were reviewed. The median age was 68 years, and the male to female ratio was 1.5:1. Final diagnosis was basal cell carcinoma (BCC) in 901 patients (78%), squamous cell carcinoma (SCC) in 242 patients (21%), and basosquamous carcinoma in 11 patients (1%). Seven hundred twelve (62%) were biopsy proven. Comparison of clinical and histologic diagnoses showed that BCC were correctly diagnosed clinically in 85% of cases but only 53% of SCC were correctly diagnosed. The distribution of sites was as follows: head and neck 871 (75%), limbs 131 (11%), trunk 50 (4%), and multiple sites 102 (9%). One thousand eighty-nine (94%) had primary lesions and 65 (6%) had recurrent lesions. The lesions were treated with surgery in 55% of cases, superficial radiotherapy in 39%, other types of radiotherapy in 3%, cryotherapy in 1%, and 5-fluorouracil in 0.2%. Recurrent lesions, lesions on the eyelids, ears or nose, and T4 lesions were significantly associated with increased failure rates. Superficial radiotherapy was associated with a 2.3-fold increase in failure rate compared to surgery when other prognostic factors were taken into account (P = 0.01, 95% confidence interval = 1.2-4.3). Nonsuperficial radiotherapy was associated with an 11.5-fold increase in failure rate compared to surgery (P less than 0.0001, 95% confidence interval = 4.9-27.1), but several of these cases were treated for palliative purposes only. The results of, and indications for treatment with surgery or radiotherapy at PMCI are discussed.
The application of a computer-assisted, three-dimensional reconstruction procedure for serial sections to embryonic rat hearts during the period of cardiac looping and compartmentalization is described. The procedure relies on immunohistochemical staining for the introduction of selective contrast and on episcopic and diascopic images of each of the sections for alignment and correction of compression due to sectioning. Episcopic (reference) images are taken from the embedding block just before the cutting of a slice and are still aligned and undeformed. Diascopic images are taken from the sections after immunohistochemical processing and, hence, contain selective contrast but are deformed and no longer aligned. The three-dimensional images are visualized as shaded voxel models. This approach allowed the unequivocal delineation of the developing myocardium and the inspection of its changing architecture both from the outside and from within. Furthermore, it allowed a quantification of myocardial volume. Because standardized and hence comparable views of three different stages were generated, changes in the shape of the cardiac loop, the atria, and the ventricles as well as changes in the position of the atrioventricular canal and interventricular foramen could be accurately described. Characteristic changes in the position of both the right ventricle and the atrioventricular canal that are essential for the formation of a correctly functioning four-chambered heart could be observed. These changes in shape occur while the myocardial size increases dramatically.
The distribution pattern of a periportal enzyme (carbamoylphosphate synthetase) and a pericentral enzyme (glutamine synthetase) in human and rat liver has provided an objective parameter to delineate the zonal boundaries of the liver acinus. On sections, the pericental zone (zone 3) is circular and discrete rather than star-like and reticular, as predicted by the acinar concept, whereas the periportal zone (zone 1) is reticular, i.e. contiguous between adjacent acini rather than discrete. Three-dimensionally, the composite of pericentral zones (the pericentral compartment) follows the branching pattern of the terminal hepatic (central) vein, whereas the composite of periportal zones (the periportal compartment) envelops the pericentral compartment as a three-dimensional network (reticulum). This modified concept that is based upon the three-dimensional distribution of hepatocyte-specific enzymes is supported by data from the literature regarding the three-dimensional angioarchitecture of the liver, the perfusion pattern of the liver and the three-dimensional pattern of tissue oxygenation. Hence, a unified concept of the liver architecture that is based upon the observed distribution pattern of blood flow, of gene expression and of metabolism can be established.
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Etomidate was used in eight patients to control status epilepticus which had been refractory to previous anticonvulsant therapy. Cortical activity was measured using a Cerebral Function Analysing Monitor and etomidate administered to achieve a 5 microV mean amplitude, avoiding burst suppression if possible with obliteration of any paroxysmal increase in amplitude. Neuromuscular blockade facilitated endotracheal intubation and mechanical ventilation, and corticosteroid replacement was provided. Rapid control of seizure activity, with cardiovascular stability, was obtained in all cases. Initially the mean infusion rate of etomidate required to achieve adequate suppression of cortical activity was 25 micrograms kg-1 min-1, but several patients exhibited tachyphylaxis. Weaning from the infusion presented difficulties in four patients due to recurring seizures. Adrenocortical function returned to normal within 96 hrs of stopping the infusion. At six month follow up, two patients had died, and two patients had significant reduction in cerebral function compared with their pre-morbid state.
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We report the isolation of a fusion hybrid, PR3, from a pluripotent embryonal carcinoma (EC) cell line, PSA4, which is metabolic cooperation-competent, and an EC line R5/3OA which has a reduced capacity for metabolic cooperation and a restricted developmental capacity. PR3 resembles its pluripotent parent PSA4 in its capacity for gap-junction-mediated transfer of uridine nucleotides and in its pluripotency both in embryoid bodies in vitro and in tumors in vivo. This enabled the relationship between pluripotency and metabolic cooperation to be examined by the selection of segregant lines. Cooperation-deficient lines were isolated from a thioguanine-resistant intermediate line (PR3Tg12) using "Kiss of Death" selection. A novel method was devised for the selection of differentiation-deficient segregants using feeder cell-conditioned medium which partially inhibits in vitro differentiation. It was found that communication-competence and in vitro pluripotency segregated independently, demonstrating that the loss of developmental capacity in R5/3OA cannot be attributed to its communication-deficiency.
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Whether thyroid replacement therapy can trigger cardiac arrhythmias in patients with hypothyroidism is not known. In this prospective study, 24 h ambulatory electrocardiographic (ECG) monitoring was used to assess the frequency of atrial and ventricular premature beats in 25 patients with hypothyroidism (5 men and 20 women, aged 56 +/- 3 years) before and 3.5 +/- 0.5 months (mean +/- SEM) after thyroid replacement therapy. Plasma thyroid-stimulating hormone was 73.6 +/- 12.3 and 3.1 +/- 0.6 microU/ml and free thyroxine index was 2.4 +/- 0.4 and 9.8 +/- 0.9 micrograms/100 ml at baseline and after thyroid replacement therapy, respectively. The frequency of ventricular premature beats was not affected by thyroid replacement therapy (from 273 +/- 221 at baseline to 352 +/- 235 beats/24 h after therapy), even in patients with frequent baseline arrhythmias. In contrast, the frequency of atrial premature beats was slightly increased after thyroid replacement therapy (from 47 +/- 17 to 279 +/- 197 beats/24 h), largely as a result of changes seen in three patients. No patient developed new onset of sustained ventricular or supraventricular arrhythmias. Average, basal and maximal heart rates during ECG monitoring increased significantly after thyroid replacement therapy (average 72 +/- 2 to 80 +/- 2; basal 64 +/- 2 to 70 +/- 2; maximal 114 +/- 3 to 130 +/- 3 beats/min, respectively, p less than 0.001). In conclusion, thyroid replacement therapy is safe in patients with common benign cardiac arrhythmias, and does not trigger an increase in arrhythmia frequency except in rare patients with baseline atrial premature beats. It is, however, associated with an increase in basal, average and maximal heart rates.
Continuous injection of L-pyroglutamate (L-PGA) into the rat striatum induces a lesion with three regions: a necrotic core, a rim of pyknotic cells, and a peripheral spongiose region. The L-PGA was administered through an implanted intrastriatal cannula coupled to an Alzet osmotic pump loaded with one of three doses of L-PGA (3, 5, or 13 times the normal amount of L-PGA/g wet wt rat forebrain (23 nmol/g). The magnitude of the lesion was dependent upon the concentration of buffered L-PGA and the duration of continuous pumping. The necrotic region contained macrophages and neutrophils, while condensed neurons and oligodendroglial cells were present in the pyknotic region. The spongiose region contained vacuolated neuropil and degenerating nerve cells and oligodendroglia. The spongiose region blends with the normal neuropil. A population of aspiny neurons were identified throughout the spongiose region. These neurons stained positive for NADPH diaphorase and demonstrated a somatostatin-like immunoreactivity similar to that of the aspiny neurons spared in Huntington's disease and in the neurotoxin-induced striatal-lesioned rat models of Huntington's disease.
The metabolism of an intravenous (IV) fat emulsion was investigated by the combination of chemical balance and computerized indirect calorimetry techniques in 21 newborns (birth weight, 3.0 +/- 0.1 kg; mean +/- SE). All babies were appropriate for gestational age and received total parenteral nutrition after a major surgical procedure. The study was divided into two consecutive periods. Phase 1 consisted of infusion of 10% glucose and 2% amino acid solutions for 24 hours, and phase 2 involved the "Intralipid utilization test" (isocaloric and isovolemic infusion of Intralipid 10% for four hours). The caloric intake was 67.1 +/- 1.9 kcal/kg/d during both phases of the study. The resting energy expenditure was 44.8 +/- 1.6 and 46.5 +/- 1.8 kcal/kg/d during phases 1 and 2 respectively. During glucose/amino acid infusion, 12 patients oxidized endogenous fat, and de novo lipogenesis from glucose was observed in nine. During the Intralipid infusion, there was a significant and progressive decrease of carbon dioxide production, respiratory quotient, and carbohydrate utilization (oxidation plus conversion to fat). Net lipogenesis ended and fat utilization significantly increased. By the second hour of Intralipid infusion, 58% of energy expenditure was derived from fat oxidation. The drop in carbon dioxide production correlated positively with the decrease in carbohydrate utilization (r = .07; P less than .001). During the third and fourth hours of phase 2, the percentage of fat utilized was negatively correlated with the amount of fat given (r = -.07; P less than .01). The surgical neonate showed rapid metabolic adaptation to Intralipid infusion.(ABSTRACT TRUNCATED AT 250 WORDS)
To determine if liver dysfunction in children affects energy and macronutrient homeostasis, we performed 13 metabolic studies in 11 patients (age, 17.8 +/- 5.9 months [mean +/- SEM]) with extrahepatic biliary atresia (EHBA). Nutritional balance, indirect calorimetry, anthropometry, and biochemical liver function tests were utilised. Sixty-four percent of the energy losses were in the form of stool fat. Energy expenditure (68 kcal/kg/d) was 29% higher than normal (P less than 0.0025). Only one third of the metabolisable energy intake (37 kcal/kg/d) was stored in the body for new tissue synthesis. In spite of the bountiful protein intake for age, the increased protein oxidation (2g/kg/d) resulted in a virtually zero mean nitrogen balance. In addition, four patients oxidised endogenous protein as well. The respiratory quotient was 0.96, and did not change significantly between pre- and post-meal measurements, suggesting a predominant utilisation of carbohydrate for energy metabolism. Net lipid oxidation was severely diminished. We found that the higher the serum aspartate aminotransferase level (previously named SGOT), the lower the net fat oxidation, and the higher the conversion of glucose to fat. These data suggest that markedly increased energy expenditure contributes to the malnutrition of patients with EHBA. We characterised for the first time how severe liver disease in infants and children affects carbohydrate, fat, and protein metabolism, thus inducing protein-energy malnutrition.
The purpose of this study was to better define the energy and macronutrient balance of infants after major surgery. Forty studies were conducted in 29 full-term surgical infants (mean weight, 3.27 +/- 0.19 kg; mean days postsurgery, 8 +/- 1). Nineteen infants were receiving total parenteral nutrition, 13 were orally fed, and eight received a combination of intravenous and oral nutrition (mean caloric intake, 84 +/- 4 kcal/kg/d). Each study was comprised of a three-day nutritional balance measuring energy intake and energy losses in excreta. Metabolizable energy intake (MEI) was determined by subtracting losses from gross intake. Energy expenditure and macronutrient oxidation were determined on the second day of the balance using continuous open-circuit indirect calorimetry in combination with timed urinary nitrogen excretion. Energy and macronutrient storage were calculated by subtracting oxidation and losses from measured intake. The mean global energy expenditure was 57 +/- 1 kcal/kg/d. Linear regression analysis of the nutritional balance data allowed estimates of energy, fat, and protein storage at various MEI. The data suggest that in the surgical infant, protein balance is maintained, even during hypocaloric nutritional regimens. In infants receiving adequate calories to maintain energy balance, maintenance metabolism is supported by the oxidation of endogenous fat. Net fat deposition will predictably only occur at metabolizable intakes of greater than 71 kcal/kg/d.
Recognition of prodromal symptoms of schizophrenia offers the potential of early intervention to avert relapse and re-hospitalization (Carpenter & Heinrichs, 1983). The present study investigated how a strategy to detect prodromal signs might be effectively applied in the clinical setting. A standard monitoring system was developed involving completion of a new early signs scale (ESS) measuring changes in key symptoms phenomenologically (self-report) and behaviourally (observer report). The ESS was subject to rigorous psychometric evaluation and tested in a prospective pilot investigation. The ESS reliably identified early signs and predicted relapse with an overall accuracy of 79%. Several different patterns of relapse were identified. Observer reports compensated for loss of insight in some patients. In two cases where early signs indices were detected, prompt increases in medication appeared to arrest relapse and avert readmission. The ESS offers itself as a reliable, valid and administratively feasible measure and demonstrates considerable potential as a cost-effective procedure for secondary prevention.
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The factor structure of the Beck Depression Inventory (BDI) was examined in an initial sample of 407 patients and replicated in a sample of 370 patients, using principal components analysis and varimax rotation. The entire sample was 98% male, with ages ranging from 22 to 88 years. The incidence of alcoholism was 72%, and the incidence of major mental illnesses was 17%. The stable dominant first factor (cognitive) accounted for 67 to 81% of the common variance, with a correlation of .94 between the factor loadings in the initial and replication analyses. The unstable second factor (vegetative) accounted for 15% to 19% of the common variance, with a correlation of .58 in item loadings. Consequently, the BDI appears to measure the cognitive aspects of depressive severity in a global fashion, as Beck originally intended. Approximately half of the items contribute very little useful predictive information. The fact that BDI total scores are not strongly related to the traditional vegetative symptoms of depression used in psychiatry is an artifact of the original method used to construct the test and is not a statement about the fundamental characteristics of depression.