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Background Delirium is a serious postoperative condition for which few pharmacologic prevention trials have been conducted. Objective The authors tested the efficacy of perioperative olanzapine administration to prevent postoperative delirium in elderly patients after jointreplacement surgery. Method The authors conducted a randomized, double-blind, placebocontrolled, prophylaxis trial at an orthopedic teaching hospital, enrolling 495 elderly patients age ≥65 years, who were undergoing elective knee- or hip-replacement surgery; 400 patients received either 5 mg of orally-disintegrating olanzapine or placebo just before and after surgery. The primary efficacy outcome was the incidence of (DSM-III-R) delirium. Results The incidence of delirium was significantly lower in the olanzapine group than in the placebo group; this held true for both knee- and hip-replacement surgery. However, delirium lasted longer and was more severe in the olanzapine group. Advanced age, a high level of medical comorbidity, an abnormal albumin level, and having knee-replacement surgery were independent risk factors for postoperative delirium (Clinicaltrials.gov Identifier: NCT000699946). Conclusion Administration of 10 mg of oral olanzapine perioperatively, versus placebo, was associated with a significantly lower incidence of delirium. These findings suggest that olanzapine prophylaxis of postoperative delirium may be an effective strategy.

Viral gene transfer or transgenic animals are commonly used technologies to alter gene expression in the adult brain, although these approaches lack spatial specificity and are time consuming. We delivered plasmid DNA locally into the brain of adult C57BL/6 mice in vivo by voltage-and current-controlled electroporation. The low current-controlled delivery of unipolar square wave pulses of 125 mu A with microstimulation electrodes at the injection site gave 16 times higher transfection rates than a voltage-controlled electroporation protocol with plate electrodes resulting in currents of about 400 mA. Transfection was restricted to the target region and no damage due to the electric pulses was found. Our current-controlled electroporation protocol indicated that the use of very low currents resulting in applied voltages within the physiological range of the membrane potential, allows efficient transfection of nonviral plasmid DNA. In conclusion, low current-controlled electroporation is an excellent approach for electroporation in the adult brain, i.e., gene function can be influenced locally at a high level with no mortality and minimal tissue damage.

Objectives: This study was conducted to compare continuous cardiac output (CCO) with bolus thermodilution cardiac output (BTD) at steady state, and to compare the response time of STAT CCO with that of trend CCO, mean arterial pressure, and mixed venous oxygen saturation (SvO2) during an acute hemodynamic change. Design: Prospective study. Setting: University hospital. Participants: Twenty-nine patients undergoing cardiac surgery or liver transplantation. Interventions: STAT and trend CCO were compared with BTD cardiac output during steady state intraoperatively and postoperatively in the intensive care unit. Ten patients, who required epicardial pacing after cardiac surgery, were studied to compare the response time of STAT CCO with that of trend CCO, mean arterial pressure, and SvO2 after a 10% to 20% increase in pacing rate. Measurements and Main Results: A total of 108 cardiac output data sets were analyzed at steady state. Steady state was defined as stable heart rate and mean arterial pressure (±5%) and stable central venous pressure (±2 mmHg) measured immediately before and after each data set. Cardiac output ranged from 2.3 to 8.5 L/min. The correlation between STAT CCO and BTD was r = 0.94, and for trend CCO and BTD was r = 0.94. The bias and precision for STAT CCO versus BTD were 0.06 L/min (CI 95%: −0.06 to 0.18) and 0.61 L/min. The bias and precision for trend CCO versus BTD were 0.06 L/min (CI 95%: −0.04 to 0.16) and 0.49 L/min. Eleven data sets were analyzed to study response time of STAT CCO, which was defined as the first time the percent change of the mean of each variable was significantly increased from baseline. Significant increases in mean arterial pressure and SvO2 were detected after 30 seconds (2.5%, p = 0.01) and 90 seconds (2.0%, p = 0.04), respectively. A significant increase in STAT CCO was reached at 270 seconds (4.4%, p = 0.006). Trend CCO tended to increase but did not reach statistical significance within 6 minutes. Conclusions: STAT and trend CCO are accurate and precise and show close agreement with BTD cardiac output at steady state. The faster algorithm of STAT CCO offers some advantage over trend CCO during an acute hemodynamic change. However, because of the averaging process for determining CCO, the response time of STAT CCO is slower than that of mean arterial pressure and SvO2.

A three-stage process starting with the deposition of (In,Ga) 2 Se 3 precursor films has been successful in the fabrication of graded band-gap Cu(In,Ga)Se 2 thin films. In this work we examine (1) the reaction of Cu + Se with (In,Ga) 2 Se 3 , which leads to a spontaneous grading in the Ga content as a function of depth through the film, and (2) modification of the Ga content in the surface region of the film through a final deposition of In + Ga + Se. We show how band-gap grading can be enhanced by the formation of non-uniform precursors, how counterdiffusion limits the degree of grading possible in the surface region, and how the Cu x Se secondary phase acts to homogenize the film composition.

Kallmann syndrome is characterized by hypogonadotropic hypogonadism and anosmia. Autosomal dominant, autosomal recessive, and X-linked patterns of transmission have been described. The X-linked form of Kallmann syndrome (XLKS) is the least common of the three modes of inheritance and is caused by mutations in the putative cell adhesion protein, KAL-1. In a large pedigree with XLKS, direct sequencing of the KAL-1 gene revealed a duplication of 11 base pairs in exon 1, resulting in a frameshift and a premature stop at codon 34 of the 680 amino acid protein. The clinical features of the affected individuals in this pedigree provide further evidence in support of the idea that XLKS is associated with neurologic features that are not seen in other forms of the syndrome.

Bronchial carcinoid tumors (BCT) are the most frequent primary pulmonary neoplasms of childhood. Seventeen of 208 patients diagnosed as having BCT at the Massachusetts General Hospital were between 10 and 21 years of age. We reviewed our records of the 17 patients and 8 other pediatric cases and compared their findings with those of seven large series of adults. Distribution was equal between the sexes. The average age at diagnosis was 17 years; 4 patients wereor = 15 years old. The duration of symptoms prior to diagnosis varied from 2 weeks to 2.6 years, with a median duration of 8.5 months. In contrast to adults, no child was asymptomatic. The majority of children presented with wheezing and atelectasis in addition to the characteristic adult triad of cough, hemoptysis, and pneumonitis. Five patients presented with weight loss and one patient presented with hoarseness. One of the 17 pediatric patients presented with Cushing's syndrome and a functional BCT. Twelve of 14 patients were disease free for 9 months to 34 years after surgical resection. We conclude that BCT should be suspected in children with pneumonitis resistant to therapy, atelectasis, wheezing, and hemoptysis. Surgical resection will result in symptom-free recovery in the majority of cases in spite of low-grade malignancy.

Zusammenfassung Fur Ein- und Zweiplattengerate mit Schutzring wird das Temperaturfeld im Probekor-per fur kreisformige und quadratische Platten berechnet und hieraus der Fehler abgeleitet, der durch den Warmeaustausch am auβeren Rand des Schutzringes bei isothermen Heiz- und Kuhlplatten und idealem Warmekontakt entsteht. Der Fehler erweist sich als proportional zur reduzierten Temperaturdifferenz (Differenz zwischen mittlerer Probekorpertemperatur und Umgebungstemperatur geteilt durch Temperaturdifferenz zwischen Heiz- und Kuhlplatte), wodurch der Randfehler durch entsprechendes Einstellen der Umgebungstemperatur optimal verlkeinert werden kann. Experimente an einem Extruderschaum bestatigen die Folgerungen der rechnerischen Analyse. Fur Plattengerate gebrauchlicher Groβen ermoglichen Diagramme und Tabellen, die aufgrund der abgeleiteten Beziehungen berechnet wurden, eine Randfehlerabschatzung der jeweiligen Meβanordnungen.

An 8 month old girl presented with undiagnosed non-anatomic congenital cardiomyopathy with massive cardiomegaly on chest X-ray film. Her older sibling had died suddenly at 6 months of age from what appeared to be a similar abnormality. Utilizing phosphorus-31 nuclear magnetic resonance (P-31 NMR) surface coil spectroscopy, a metabolic disorder was demonstrated in both her myocardium and skeletal muscle, revealing a phosphocreatine (PCr) to inorganic phosphate (Pi) ratio of half of that for a normal control infant. Manipulation of serum substrate availability indicated that medium chain triglycerides alone did not improve myocardial metabolism, but that intravenous glucose or oral carbohydrate loading raised the myocardial PCr/Pi ratio from 1.0 +/- 0.05 to 1.8 +/- 0.1 (p less than 0.01) without significantly affecting the PCr/Pi value of her resting skeletal muscle. This study demonstrates the feasibility of using P-31 nuclear magnetic resonance to evaluate the biochemistry of the human myocardium in vivo and to diagnose a metabolic abnormality. Phosphorus-31 nuclear magnetic resonance can thus be used to optimize therapy for human disease.

The correlationbetween proteinturnoverand serum thyroidhormone levelswas studied in 10children,ages I to 16 yearssubsequent tosevereburn injuries. In contrast to published studies that have shown depression of triiodothyronine (Ti) and elevations of reverse Ti (rT:,) in stressed patients, no change was found in the mean level of Ti and a 69% decrease in rT:, compared to healthy controls of similar age. Whole body rates of protein synthesis and breakdown were determined using a I'5N)glycine turnover technique. The difference between synthesis and break- down was negatively correlated with the ratio, rT,/T, in serum. Thus, in burned children, a decrease in N balance was associated with a rise in rT3/T:, which is qualitatively similar to that observed in fasted individuals or in stressed patients who may be semistarved. Am. J. C/in. Nuir. 33: 1215-1219, 1980.

The rates of glucose production and utilization can be estimated by a primed-constant infusion technique using separate catheters for the infusion of radiolabelled glucose and periodic blood withdrawal. In rats, a carotid artery catheter is most often combined with a jugular or femoral venous catheter in such studies. We presently describe a method which utilizes a single jugular catheter for both infusion and sampling in the awake rat. This method is directly compared with simultaneous carotid artery sampling during both the dynamic steady state and a nonsteady state induced by a constant infusion of insulin. Our results demonstrate the validity of a single vein design for the analysis of glucose kinetics in either state. Rapid sampling and complete flushing prevent disruption of infusate equilibrium and sample contamination respectively. This single catheter method requires less technical skill for placement, reduces surgical intervention and enhances the comfort of the awake rat.

Goiters are rarely palpable in infants with congenital hypothyroidism except in the case of maternal ingestion of iodide. The presence or absence of glandular tissue is, however, important for genetic and prognostic counseling and for acceleration of diagnosis in other affected siblings. The detection of thyroid tissue by /sup 99m/Tc pertechnetate scans in a significant number of our patients heretofore considered athyreotic establishes that physical findings and traditional laboratory data are not adequate to determine whether or not thyroid tissue is present.

The therapeutic efficiency of Chlorpropamide was evaluated in three patients with hypodipsia and diabetes insipidus. Hitherto extraordinarily difficult management problems, the patients responded with recovery of homeostatically appropriate thirst, improved renal concentrating ability and normalization of serum tonicity. Tests of their responses to fluid loading and water restriction indicated that normotonicity was protected during treatment through wide ranges of fluid intake varying from 2.2 to 5.0 L/twenty-four hours. Over a period of one year of treatment the patients have maintained normal fluid and electrolyte homeostasis despite abandonment of the strict fluid and diet regimens previously required to prevent wide swings in tonicity. Evidence is cited in support of the tenet that the beneficial effect of the sulfonylureas at the renal level depends upon amplification of the response of the adenyl cyclase system to residually low but facultatively controlled levels of vasopressin. The reappearance of appropriate drinking behavior during chlorpropamide treatment is probably similarly mediated, being attributable to a step-up of attenuated neural discharges by an effect of the drug on nucleotide system(s) in the brain.

The observation that dexamethasone given normal individuals as a single dose at midnight results in low levels of plasma cortisol at 8:00 a.m., presumably by inhibiting the early-morning pituitary discharge of ACTH, stimulated investigation of the therapeutic value of dexamethasone so administered to patients with congenital adrenocortical hyperplasia. Detailed studies on four patients are presented. Results of short-and long-term treatment suggest that single, appropriately timed doses of 0.25 to 0.75 mg daily cause normalization of urinary 17-ketosteroid and pregnanetriol output, provide sufficient daily glucocorticoid for bodily needs, and simplify therapy for this disorder in adults and adolescents who have reached their mature height.

A 17-year-old girl was admitted for evaluation of short stature, delayed puberty, diabetes mellitus, and hepatomegaly. The patient was well until age 14 months when she presented with diabetic ketoacidosis. At five years of age, she was hospitalized twice for ketoacidosis with upper respiratory infections. She was noted to have hepatomegaly, but had normal liver function studies. The short stature had been recognized, but her parents were informed that subnormal growth was typical of children with diabetes. Because the family moved frequently, at least 12 different pediatricians were consulted. For the five years prior to our evaluation, the patient had been ireated With 12 units each of NPH and regular insulin daily. She and her parents claimed that mild ketonuria and increased glucosuria had been noted only over the past two months. physical examination showed (Fig. 1) a very small, younger appearing girl with a protuberant abdomen, weighing 31.5 kg with a height of 132 cm. Blood pressure measured 120/78 mm Hg; pulse rate was 84/minute. The fundi showed mild Venous dilatation but no other changes consistent with diabetic retinopathy. The thyroid, heart, and lungs were normal. The abdomen was distended by an enlarged smooth, nontender liver, 14 cm in vertical span. Pubertal development was at Tanner Stage II. Hair growth was increased on the extensor surfaces of all extremities, and the fourth and fifth fingers bilaterally had flexion contractures. Lipodystrophy was evident at the insulin injection sites. No neurologic deficit was apparent. The hemogram was normal. Glucose and ketones were present in the urine. The patient had normal serum electrolyte, creatinine, and blood urea nitrogen concentrations; blood glucose