Reduced Serum Theophylline Concentrations after Discontinuation of Azithromycin: Evidence for an Unusual Interaction

A 68-year-old man receiving long-term therapy with oral sustained-release theophylline 450 mg twice/day was admitted to the hospital after failing treatment with azithromycin for an acute exacerbation of obstructive lung disease. Peak serum theophylline concentration was 20 μg/ml (normal 10–20 μg/ml). Azithromycin was discontinued and the theophylline dosage reduced by 33%. The subsequent 80% decrease in serum theophylline to 4.6 μg/ml was unexpectedly large. Two rechallenges produced similar transient depressions of serum theophylline concentrations after withdrawal of azithromycin, suggesting an interaction. Withdrawal of azithromycin may leave an increased number of active enzyme sites available as the drug is cleared from the system. In some circumstances, it may be useful for pharmacokinetic interaction studies to continue measuring concentrations after the suspected interacting agent is stopped.     

Nephrectomy during operative management of retroperitoneal sarcoma

Background: Complete resection of a retroperitoneal sarcoma often requires removal of adjacent organs. In this study we evaluated the role of nephrectomy during operation for retroperitoneal sarcoma. Methods: Between July 1982 and July 1995, 75 of the 371 (20%) patients who underwent resection of retroperitoneal sarcoma at MSKCC underwent concommitant nephrectomy. Data concerning the reasons for nephrectomy, degree of sarcomatous renal involvement, and survival were retrospectively analyzed. Results: Fifty-four patients (72%) underwent nephrectomy during the initial resection, and 21 (28%) during a resection of a recurrent or persistent tumor. The most common reason for nephrectomy was total encasement by sarcoma (n=40; 53%), followed by dense adherence of the tumor to the kidney (n=21; 28%), and the direct invasion of the kidney by tumor (n=2; 3%). Pathology demonstrated an absence of kidney invasion in the majority of cases (55 of 75; 73%). Renal capsular invasion was present in 11 of 75 (15%), renal parenchymal invasion in 7 of 75 (9%), and renal vein invasion in 2 of 75 (3%) of cases. There were no significant differences in survival based on degree of sarcoma involvement of the kidney, tumor grade, or whether the resection was for primary or recurrent disease. The 53 patients who underwent a complete gross resection of all tumor had a significantly improved long-term survival compared to the 20 patients who did not (50% versus 20% DFS at 5 years, respectively; p<0.001). Conclusions: Decisions for concomitant nephrectomy during resection of retroperitoneal sarcoma should be based on whether this maneuver will provide a complete resection of all gross tumor, in which case the long-term disease-free survival of 50% is comparable to the reported 5-year survival of all patients with retroperitoneal sarcoma who are completely resected. Presented at the 49th Annual Cancer Symposium of the Society of Surgical Oncology, Atlanta, Georgia, March 21–24, 1996.     

Metabolic and hemodynamic responses to concurrent voluntary arm crank and electrical stimulation leg cycle exercise in quadriplegics.

This study determined the metabolic and hemodynamic responses in eight spinal cord injured (SCI) quadriplegics (C5-C8/T1) performing subpeak arm crank exercise (ACE) alone, subpeak functional electrical stimulation leg cycle exercise (FES-LCE) alone, and subpeak FES-LCE concurrent with subpeak ACE (hybrid exercise). Subjects completed 10 minutes of each exercise mode during which steady-state oxygen uptake (VO2), pulmonary ventilation (VE), heart rate (HR), cardiac output (CO), stroke volume (SV), mean arterial pressure (MAP), arteriovenous oxygen difference (a-v O2 diff), and total peripheral resistance (TPR) were determined. Although mean VO2 for both ACE alone and FES-LCE alone was matched at 0.66 l/mi, individualized power outputs ranged from 0-30 W (mean = 19.4 +/- 1.3) and 0-12.2 W (mean = 2.3 +/- 0.6), respectively. Hybrid exercise elicited significantly higher VO2 (by 54 percent), VE (by 39-53 percent), HR (by 19-33 percent), and CO (by 33-47 percent), and significantly lower TPR (by 21-34 percent) than ACE or FES-LCE performed alone (P less than or equal to 0.05). Stroke volume was similar between hybrid exercise and FES-LCE alone, and these two exercise modes evoked a significantly higher SV (by 41-56 percent) than during ACE alone. These data clearly demonstrate that hybrid exercise creates a higher aerobic metabolic demand and cardiac-volume load in SCI quadriplegics than either subpeak levels of ACE or FES-LCE performed separately. Therefore, hybrid exercise may provide more advantageous central cardiovascular training effects in quadriplegics than either ACE or FES-LCE alone.     

Quality of life in surgically palliated complex congenital heart disease.

The outcome of surgical palliation was evaluated in 26 children with complex cyanotic congenital heart disease. Outcome was examined in terms of ongoing symptoms, exercise tolerance, and the ability to participate in normal childhood activities. An activity score was calculated and each child performed graded treadmill exercise testing. Breathlessness (24 (92%) children), respiratory infections (nine (35%) children), and leg cramps (eight 31%) children) were the most common physical disorders. Although formal exercise testing showed a clear reduction in exercise tolerance compared with age and sex matched controls, palliation had allowed 23 (89%) to function with moderate exercise limitation, three (11%) having severely limited activity. Parents underestimated the child's exercise tolerance in 80% of cases. Sixteen (62%) patients attended school full time, eight (31%) attended part time, and two (8%) received only home tuition. Palliative surgery can give children with a single functional ventricle a level of activity which allows them to take part in most childhood activities. Subjective estimates of exercise tolerance are inaccurate in this group of children, and formal exercise testing can contribute useful information to decision making about further surgical intervention.     

Increased salt retention and hypertension from non-steroidal agents in the elderly

We studied blood pressure and natriuretic responses to acute salt loading, and the effect of non-steroidal anti-inflammatory agents on these responses, in five healthy normotensive women aged 65 to 71 years. Five women aged 25 to 31 years acted as controls. Intravenous saline loading, with and without prior ingestion of ibuprofen, was 15 ml/kg/h for 3 h. Baseline blood pressures were higher in the elderly. Saline infusion without ibuprofen raised systolic blood pressure (SBP) by about 25 mmHg in the older group only. Ibuprofen increased baseline SBP in the elderly (129 +/- 6 vs. 116 +/- 5 mmHg, p < 0.05). Saline loading after ibuprofen again raised blood pressure by about 25 mmHg in the elderly only. The elderly group showed markedly increased sodium excretion during saline loading, but this was reduced by ibuprofen. Ibuprofen had no effect on SBP or sodium excretion in controls. Ageing appears to increase susceptibility to salt retention and hypertension from non-steroidal anti-inflammatory agents.      

Cerebral vascular effects of angiotensin II: new insights from genetic models.

Very little is known regarding the mechanisms of action of angiotensin II (Ang II) or the consequences of Ang II-dependent hypertension in the cerebral circulation. We tested the hypothesis that Ang II produces constriction of cerebral arteries that is mediated by activation of AT1A receptors and Rho-kinase. Basilar arteries (baseline diameter approximately 130 microm) from mice were isolated, cannulated and pressurized to measure the vessel diameter. Angiotensin II was a potent constrictor in arteries from male, but not female, mice. Vasoconstriction in response to Ang II was prevented by an inhibitor of Rho-kinase (Y-27632) in control mice, and was reduced by approximately 85% in mice deficient in expression of AT1A receptors. We also examined the chronic effects of Ang II using a model of Ang II-dependent hypertension, mice which overexpress human renin (R+) and angiotensinogen (A+). Responses to the endothelium-dependent agonist acetylcholine were markedly impaired in R+A+ mice (P<0.01) compared with controls, but were restored to normal by a superoxide scavenger (PEG-SOD). A-23187 (another endothelium-dependent agonist) produced vasodilation in control mice, but no response or vasoconstriction in R+A+ mice. In contrast, dilation of the basilar artery in response to a NO donor (NONOate) was similar in R+A+ mice and controls. Thus, Ang II produces potent constriction of cerebral arteries via activation of AT1A receptors and Rho-kinase. There are marked gender differences in cerebral vascular responses to Ang II. Endothelial function is greatly impaired in a genetic model of Ang II-dependent hypertension via a mechanism that involves superoxide.     

Noninvasive Estimation of Blood Alcohol Concentrations: Ethanol Vapor Above the Eye

The present study describes, in animals, a novel approach to the in vivo, noninvasive determination of alcohol in the body. The concentration of ethanol in vapor above the lacrimal fluid in the eye was analyzed in situ by the use of a fast (1-min) gas sensor method developed previously for biological liquids. After an oral dose of 1 g/kg to 11 animals, eye vapor measurements and blood samples were obtained over 4 hr. The correlation of 61 blood ethanol concentrations obtained by the two methods yielded a correlation coefficient of 0.92 and a slope of 0.99. The metabolic rates of ethanol determined by gas chromatographic analysis of blood and by ethanol eye vapor analysis are virtually identical. The data suggest that ethanol eye vapor analysis may be an attractive, noninvasive method for the determination of ethanol in animals. The method is not subject to false high readings due to alcohol in the buccal cavity and thus might constitute an alternative to breath analysis in the human. In a separate series, ethanol was determined by head space gas chromatography in samples of blood and lacrimal fluid while the animals were under ketamine anesthesia. The correlation of ethanol concentrations in blood and lacrimal fluid (r = 0.99) shows that ethanol is distributed in lacrimal fluid which comprises part of total body water.     

Event-related Potentials as Markers for Alcoholism Risk in High Density Families

One hundred sixty-eight adult siblings and parents from affected and control families were tested for ERP characteristics using two tasks involving an auditory oddball paradigm. Significant within family differences among affected families suggest that risk for developing alcoholism may be seen even in adult subjects who have had experience consuming alcohol. Further, analysis of quantity and recency of drinking in the past seven days were not correlated with either amplitude or latency of P300, suggesting that the within-family differences observed reflect relative risk for developing alcoholism rather than experience with alcohol.     

'Not everything that can be counted counts and not everything that counts can be counted'– towards a critical exploration of modes of satisfaction measurement in sheltered housing

This paper reflects on a research project funded by a consortium of leading sheltered housing (SH) providers and their regulatory body, the Housing Corporation. The project aimed to ascertain which aspects of SH older people perceived to be central to their satisfaction and the methods they judged most appropriate to measuring this. We outline key policy developments of importance to SH (specifically the development of performance measurement regimes), and changes in the nature of SH, which are driving providers to re‐evaluate how they measure user satisfaction. We discuss the aims of the project, our methodology and findings, and conclude by raising critical questions about the process of measuring satisfaction within an increasingly managerialised housing system. We argue that this favours standardised methods of information gathering (such as questionnaires) rather than engage with clients in order to develop methods and systems capable of eliciting qualitative issues of concern to them. Our conclusions are, we believe, applicable to health and social care provision, where similar tensions exist around performance measurement and user satisfaction.     

Combined Excimer Laser and Topical Tacrolimus for the Treatment of Vitiligo: A Pilot Study

Background. Vitiligo is an acquired skin disorder that is characterized by well-defined, often symmetric white patches. Although current therapeutic modalities are directed toward increasing melanocyte melanin production, few treatment modalities address the immunologic nature of the disease.
Objective. To determine whether excimer laser, a known therapeutic modality, in combination with tacrolimus, a topical immunomodulator, accelerate response time and/or improve the degree of response in patients with this disorder.
Methods. Eight subjects diagnosed with vitiligo were recruited to participate in this institutional review board–approved double-blind, placebo-controlled study. Twenty-four symmetric vitiliginous patches (elbows, knees) from eight subjects received excimer laser treatment three times per week for 24 treatments or 10 weeks. Additionally, topical tacrolimus 0.1% ointment (Protopic) and placebo (Aquaphor) were applied to randomized patches (left or right) twice daily throughout the length of the trial. Vitiliginous patches were monitored with photographs at baseline, every 2 weeks, and 6 months after treatment. Biopsies were performed on subjects with significant results.
Results. Twenty vitiliginous patches from six subjects qualified for evaluation. Fifty percent of patches treated with combination excimer laser and tacrolimus achieved a successful response (75% repigmentation) compared with 20% for the placebo group. Subjects who responded successfully repigmented faster (19%) with combination therapy compared with excimer laser alone. Additionally, three subjects experienced transient hyperpigmentation in lesions treated with combination therapy.
Conclusion. Combining topical immunomodulators with known phototherapeutic modalities may represent a key advancement in the treatment of disease.