Comparison of the blood-brain barrier and liver penetration of acridine antitumor drugs

Summary The blood-brain barrier penetration of amsacrine and its analogs 9-({2-methoxy-4-[(methylsulfonyl)-amino]phenyl}amino)-,5-dimethyl-4-acridine carboxamide (CI-921) and M-[2-(dimethylamino)ethyl]-acridine-4-carboxamide (AC) was measured in the barbiturate-anesthetized mouse. After intracarotid administration, AC was almost completery extracted (90%) in a single transit through the brain capillaries, whereas CI-921 (20%) and amsacrine (15%) were moderately extracted. AC is retained in the brain; no loss of AC from the brain was apparent at 1, 2, 4, or 8 min after injection. In contrast, after intraportal administration, 75% of the AC, 94% of the CI-921, and 57% of the amsacrine was extracted in a single transit through the hepatic vasculature. Rather than being retained in the mouse liver, these acridine antitumor agents show time-dependent loss (t _1/2=10 min for amsacrine and AC, 24 min for CI-921). We conclude that unlike most antitumor agents, these acridine drugs appear to penetrate the blood-brain barrier readily.This study was supported by the Auckland Medical Research Foundation (New Zealand), by the Medical Research Foundation (New Zealand), by the National Science Foundation (United States/New Zealand Cooperative Science Program), by the United States Veterans Administration, and by NIH grant NS 25554     

Autoamputation of the foot caused by untreated gas gangrene: a case report

Gas-producing diabetic foot infections are limb-threatening emergencies commonly encountered by foot and ankle surgeons. Appropriate treatment includes aggressive surgical debridement, parenteral antibiotics, and postoperative wound care. The authors present a unique case of a patient who refused treatment for a deep-space gas-producing infection, resulting in autoamputation of the foot. The authors also discuss the confusion surrounding the definition of gas gangrene.     

Synovial fluid levels of fluconazole in a patient with Candida parapsilosis prosthetic joint infection who had an excellent clinical response

A 73-year-old woman presenting with persistent swelling of the right knee 30 months after total joint arthroplasty was found to have a Candida parapsilosis infection. Treatment with fluconazole resulted in full recovery.     

Calcium Concentration-dependent Mechanisms through which Ketamine Relaxes Canine Airway Smooth Muscle

Background: Ketamine is a potent bronchodilator that, in clinically used concentrations, relaxes airway smooth muscle in part by a direct effect. This study explored the role of calcium concentration (Ca2+) in this relaxation.

Methods: Canine trachea smooth muscle strips were loaded with the fluorescent probe fura-2 and mounted in a spectrophotometric system to measure force and intracellular calcium concentration ([Ca2+]i) simultaneously. Calcium influx was estimated using a manganese quenching technique. Cyclic nucleotides in the airway smooth muscle strips were measured by radioimmunoassay.

Results: In smooth muscle strips stimulated with submaximal (0.1 micro Meter) and maximal (10 micro Meter) concentrations of acetylcholine, ketamine caused a concentration-dependent decrease in force and [Ca2+]i. The sensitivity of the force response to ketamine significantly decreased as the intensity of muscarinic receptor stimulation increased; the median effective concentration for relaxation induced by ketamine was 59 micro Meter and 850 micro Meter for tissue contracted by 0.1 micro Meter or 10 micro Meter acetylcholine, respectively (P < 0.05). In contrast, the sensitivity of the [Ca2+] sub i response did not depend on the intensity of muscarinic receptor stimulation. Ketamine at 1 mM significantly inhibited calcium influx. Ketamine did not significantly increase cyclic nucleotide concentrations.     

Pharyngeal Patency in Response to Advancement of the Mandible in Obese Anesthetized Persons

Background: During anesthesia in humans, anterior displacement of the mandible is often helpful to relieve airway obstruction. However, it appears to be less useful in obese patients. The authors tested the possibility that obesity limits the effectiveness of the maneuver.

Methods: Total muscle paralysis was induced under general anesthesia in a group of obese persons (n = 9; body mass index, 32 +/- 3 kg sup -2) and in a group of nonobese persons (n = 9; body mas index, 21 +/- 2 kg sup -2). Nocturnal oximetry confirmed that none of them had sleep-disordered breathing. The cross-sectional area of the pharynx was measured endoscopically at different static airway pressures. A static pressure-area plot allowed assessment of the mechanical properties of the pharynx. The influence of mandibular advancement on airway patency was assessed by comparing the static pressure-area relation with and without the maneuver in obese and nonobese persons.

Results: Mandibular advancement increased the retroglossal area at a given pharyngeal pressure, and mandibular advancement increased the retropalatal area in nonobese but not in obese persons at a given pharyngeal pressure.     

Serum and Plasma Markers of Nutritional Status in Children Infected with the Human Immunodeficiency Virus

Objective To determine whether reduced serum or plasma protein and micronutrient levels are common in children infected with the human immunodeficiency virus (HIV) and whether these levels are different in children with growth retardation compared to those with normal growth.

Subjects Children were separated into three groups: (a) HIV-infected with growth retardation (HIV+Gr); (b) HIV-infected with normal growth (HIV+); (c) HIV-uninfected with normal growth (HIV-). All children were afebrile and free of acute infection at the time of study. During a 24-hour stay in the Pediatric Clinical Research Unit, blood was drawn for analysis of total protein, albumin, zinc, selenium, and vitamin A levels; growth measurements were obtained; and dietary intake was assessed by 24-hour weighed food intake and 24-hour dietary recall.

Statistical analysis Mean differences between groups were assessed by analysis of variance, and differences in the frequency of nutrient deficiency were determined by χ² analysis.

Results Thirty-eight children between 2 and 11 years of age were studied: 10 HIV+Gr, 18 HIV+, and 10 HIV-. No statistically significantly differences were noted in mean levels of albumin, prealbumin, zinc, and selenium. Mean serum level of vitamin A was significantly higher in the HIV+Gr group than in the other two groups. There were no significant differences between groups in the frequency of deficiency for any nutrient studied. Mean energy and nutrient intake was similar among groups.

Applications/conclusions Abnormal serum or plasma protein or micronutrient levels were uncommon in this cohort of HIV-infected children, even in children with growth retardation. Routine monitoring of the level of proteins and micronutrients studied is unnecessary in the absence of specific clinical indicators of deficiency. J Am Diet Assoc. 1997-97:1377-1381.     

Gastric Bypass for Morbid Obesity: a Standard Surgical Technique by Consensus

Background: The gastric bypass operation has evolved since 1966 when it was first introduced. The purpose of this study was to determine the present state of gastric bypass by consensus among the members of the American Society for Bariatric Surgery (ASBS). Method: A questionnaire was sent to all members of the ASBS. Forty-three percent responded reporting over 41,200 cases. Results: Results were analyzed by using χ² tests with a null hypothesis. Surgeons agreed on several technical aspects, preferring a vertical to a horizontal stapleline; estimating, rather than measuring, the pouch volume at an average of 22 cc. Few surgeons divide the short gastric vessels, and only 25% of surgeons polled use a restrictive ring or band proximal to the gastroenterostomy. Most surgeons calibrate the gastroenterostomy, reporting a preferred average diameter of 12.3 cm. There was no consensus regarding forming the gastroenterostomy, 58% preferring hand-sewn and 42% stapled anastomoses. There was no consensus regarding dividing the gastric pouch from the bypassed stomach: Conclusion: The preferred gastric bypass is vertical, with the pouch estimated at 20-25 cc, and the gastroenterostomy calibrated at 12 mm diameter. The short gastric vessels need not be divided, and restrictive bands or rings are not preferred. This technique of gastric bypass should be used as the control procedure when modifications are tested in future trials. Randomized prospective studies are suggested to probe the benefits of division of the stomach pouch from the bypassed stomach.     

Estimating IQ from Adaptive Behaviour Information in People with Moderate or Severe Intellectual Disability

It is often useful in studies of intellectual disability to be able to stratify the sample in terms of intellectual level. However, this information is sometimes difficult to obtain, and can involve a great deal of time if full IQ assessments are performed. This study explores the accuracy with which IQ scores can be projected by multiple regression from adaptive behaviour scores provided by informants. Fifty-one people with moderate, severe or profound intellectual disability received IQ assessments using the Kaufman Assessment Battery, and adaptive behaviour assessments using the Adaptive Behavior Scales (ABS). Ninety percent of projected estimates differed by less than 30% from that estimated by the K-ABC. Mean percentage divergence between actual and predicted estimates of IQ for the 51 cases for which all data were available was 15.0%. Limitations of the technique are discussed. The actual coefficients for calculating IQ are given in tabular form.