Prospective prediction of post-radiation therapy lung function using quantitative lung scans and pulmonary function testing

Surgeons have made use of quantitative perfusion lung scanning (QS) and forced expiratory volume in one second (FEV1) to predict a patient's ability to tolerate lung resection. In this study QS and FEV1 were used to predict prospectively pulmonary function following lung irradiation (XRT). Twenty-two patients have had QS and FEV1 determined before XRT and at planned intervals post-XRT. Serial determination of lung function post-XRT allows comment on the temporal nature of the XRT effect on lung function. Seventeen patients had QS and FEV1 determined at an interval of 2-6 months post-irradiation with a drop in the groups mean FEV1 from 1.91 to 1.87L. or 2% during that interval. In the interval from 6-12 months post-XRT, 13 patients had studies with the groups mean FEV1 dropping from 1.79 to 1.58L or 12% of the original. In the interval from 12-18 months, 6 patients had a decline in mean FEV1 from 1.73 to 1.56L. or 10% of the original. In 22 patients a predicted final FEV1 was compared with a measured value at an interval from XRT. Fourteen of these determinations were at intervals greater than 6 months from the start of XRT and 6 at intervals of greater than 1 year. FEV1 was seen to drop during the follow-up intervals toward the predicted value. In only 2 patients did the final FEV1 drop below the predicted FEV1 and never by more than 0.12L. (6%). In summary, a method for predicting post-XRT pulmonary function using QS and FEV1 is described. Serial follow-up revealed a latent period followed by a late phase where FEV1 fell toward, but not significantly below, the predicted value. Such a determination can be of value in formulating a treatment plan for patients with significantly diminished pulmonary function.     

CT-guided biopsy for the detection and staging of tumors of the head and neck

Twenty patients underwent computed tomography (CT)-guided thin-needle biopsy of tumors of the had and neck without complication. This technique was found to have wide application in confirming the presence and extent of primary disease as well as documenting nodal and bony metastases not apparent clinically.     

Esophageal speech: double-contrast evaluation of the pharyngo-esophageal segment

Alaryngeal voice is usually accompanied by esophageal speech; however, about 40% of laryngectomy patients are unable to achieve adequate esophageal speech and must rely on mechanical devices for communication. A technique was developed for performing double-contrast studies of the hypopharynx, cervical esophagus, and pharyngo-esophageal segment using thick barium and the air normally injected for speech. Simultaneous audio and video recordings obtained during esophageal speech allowed correlation of the quality of speech with the motion of the pharyngo-esophageal segment. In 35 patients with various degrees of fluency in esophageal speech, normal and abnormal function of the pharyngo-esophageal segment was documented. Inadequate esophageal speech can be related to abnormal motion of the pharyngo-esophageal segment.     

Antibody delivery and effector cell activation in a phase II trial of recombinant gamma-interferon and the murine monoclonal antibody CO17-1A in advanced colorectal carcinoma

Murine monoclonal antibodies of the immunoglobulin G2a isotype interact with human effector cells to mediate antibody-dependent cellular cytotoxicity (ADCC) directed against malignant cells which express antigens recognized by these antibodies. gamma-Interferon enhances these effects in vitro. In a Phase I trial of murine monoclonal antibody CO17-1A and recombinant gamma-interferon (rIFN-gamma), we demonstrated that low doses of rIFN-gamma were superior to high doses in augmenting ADCC mediated by treated patients' monocytes. These results formed the basis for a Phase II trial of CO17-1A combined with low dose rIFN-gamma. Nineteen patients with metastatic colorectal carcinoma were treated with four consecutive daily infusions of 1.0 X 10(6) IU/m2 rIFN-gamma, with 150 mg of CO17-1A administered on days 2, 3, and 4. Therapy was tolerated well. Peripheral blood mononuclear cells were purified from patient samples obtained at baseline and at 1, 4, or 24 h following the start of the first rIFN-gamma infusion and were tested for their ability to lyse 111In-labeled cells of the SW1116 colorectal line. Enhancement of monocyte ADCC was seen by 24 h, while lymphocyte ADCC and natural killer activity directed against K562 cells were enhanced to a lesser extent. Nonspecific lysis of SW1116 cells by effectors was not seen at the time points examined. While CO17-1A antigen expression was observed in most biopsies, 131I-labeled CO17-1A imaged positively in less than one-half of the organs known to harbor metastases, and therapeutic antibody delivery was not always demonstrated by immunoperoxidase staining techniques of tissue obtained following therapy. In antigen-positive lesions, tissue pO2 levels appear to identify lesions which would image positively. No objective responses were seen. Our findings suggest that prolonged therapy with low doses of rIFN-gamma potentiates ADCC but that physiological obstacles to therapeutic antibody delivery are significant. In order to evaluate the validity of this therapeutic approach, measures to enhance antibody delivery are needed, starting with systematic evaluations of therapy with escalating doses of CO17-1A combined with low dose rIFN-gamma therapy.     

The Role of Behavior Modification in the Treatment of Anorexia Nervosa

This paper reviews the use of operant conditioning techniquesas an adjunct to the treatment of anorexia nervosa. Anoexianervosa appears to have a markedly variable prognosis, regardlessof the method of treatment. Operant conditioning is useful forfacilitating weight gain in anorexic patients but in no wayprevents recurrence. There is no evidence that behavioral treatmentsare harmful or result in worse outcome than other therapies.Future studies must evaluate the role of behavioral techniqueswithin the context of family therapy and must also delineatethose patients who are likely to be helped by an operant paradigmversus those for whom it is likely to be useless. Behavior therapyshould be recognized as being helpful only for the weight restorationof anorexic patients; concomitant individual and family psychotherapyis required to reduce further morbidity.     

Hypothalamic function as related to body weight and body fat in anorexia nervosa.

Percentage body fat is predictive of the onset of menstruation at puberty. In anorexia nervosa a relationship between luteinizing hormone (LH) levels and percentage weight loss has been reported. In the current study the relationship of percentage body fat and of percentage weight loss to LH and LH reactivity was examined in anorexia nervosa. Fifteen women with anorexia nervosa were studied. The resting levels of LH were measured, and in seven of the subjects LH response to luteinizing hormone releasing hormone (LHRH) and clomiphene was tested. The increment in plasma LH was measured in response to a 100 microgram dose of LHRH, and also to a 5-day course of clomiphene 100 mg. The resting LH levels were found to correlate with percentage fat, body weight, and percentage weight loss. Correlations were also found between the response to either LHRH or clomiphene and percentage weight loss, percentage fat, and absolute body weight. Other pituitary hormones measured did not show a relationship to body fat or weight. It is concluded that in addition to being predictive of the onset of menstruation, percentage body fat is significantly related to resting LH and LH reactivity in anorexia nervosa. Although percentage body fat, percentage weight loss, and absolute body weight are all significant correlates of LH reactivity, we cannot at this time conclude that any one in particular is the superior.     

Actigraphy and parental ratings of sleep in children with attention-deficit/hyperactivity disorder (ADHD)

STUDY OBJECTIVES: To assess various sleep parameters in latency-aged children with ADHD and their normally developing peers through the use of multiple sleep measures. DESIGN: Six sleep parameters were evaluated for two groups of children, ADHD and normal comparison. Each group consisted of 25 children (20 males, 5 females) who ranged in age from 7 to 11 years. All children underwent rigorous diagnostic procedures and the ADHD subjects were selected only if they displayed pervasiveness in their symptomatology and were medication naive. Parents completed a retrospective questionnaire which evaluated sleep problems over the past six months. Additionally, each child wore an actigraph for seven consecutive nights, and the child's parents completed a sleep diary during this time period. SETTING: N/A. PATIENTS or PARTICIPANTS: N/A. INTERVENTIONS: N/A. RESULTS: Based on the findings from the questionnaire, parents of children with ADHD reported significantly more sleep problems than parents of normally developing children. However, the majority of these sleep differences were not verified through actigraphy or sleep diary data, with the exception of longer sleep duration for children with ADHD and parent reports that describe increased bedtime resistence. It was also found that child-parent interactions during bedtime routines were more challenging in the ADHD group. CONCLUSIONS: Despite the possibility of intrinsic sleep problems such as longer sleep duration, results indicate that many of the sleep problems of children with ADHD may be due to challenging behaviours during bedtime routines. The reason for discrepancies among sleep studies employing objective measures as well as between retrospective and prospective measures are discussed.     

A randomized trial of the long-term, continued efficacy and safety of modafinil in narcolepsy

Objective: To assess the continued efficacy of modafinil in the treatment of excessive daytime somnolence (EDS) of narcolepsy.Background: Modafinil has been shown to be a safe and effective treatment for the EDS presented by patients with narcolepsy. However, the duration of treatment has been relatively brief, particularly considering the chronic nature of the disease.Methods: Sixty-nine patients with narcolepsy, who completed a 6-week crossover study of modafinil continued on modafinil for 16 weeks of open-label treatment (300+/-100 mg). This was followed by 2 weeks during which patients were randomly and blindly allocated to continue modafinil (M) at the same dose (n=30), or placebo (P; n=33).Results: A mean dose of 330 mg of modafinil continued to produce a significant decrease in EDS as measured by the Maintenance of Wakefulness Test (9.7+/-7.9 for P; 16.4+/-13.7 for M; P=0.009), the Epworth Sleepiness Scale (15.4+/-5.8 for P; 13.2+/-5.7 for M; P=0.023), and the number of episodes of severe somnolence and sleep reported in patient diaries (8.2+/-7.2 for P; 4.2+/-5.2 for M; P=0.017). Modafinil had no significant effects on nocturnal sleep, blood pressure, heart rate, the electrocardiogram (ECG), weight, or mood.Conclusion: Modafinil continues to be an effective and well-tolerated drug after 16 weeks of treatment.