A new measure of health status for clinical trials in inflammatory bowel disease

We have developed a measure of subjective health status (quality of life) for patients with inflammatory bowel disease (IBD). Ninety-seven patients with IBD described problems they had experienced as a result of the disease; the 32 most frequent and important items were included in the Inflammatory Bowel Disease Questionnaire (IBDQ). Sixty-one IBD patients were evaluated twice. One month separated the evaluations, at which disease activity indices, the IBDQ, and a number of other questionnaires were administered. Reproducibility studies in 19 stable patients showed improvement in scores, but also a small within-person standard deviation. Responsiveness studies revealed large changes in scores in patients who had improved or deteriorated and suggested that the IBDQ was more responsive than a general health status measure. Responsiveness appeared greater in patients with ulcerative colitis than in those with Crohn's disease. Predicted and observed correlations between changes in IBDQ score and changes in other measures were similar. We conclude that although further testing is required, particularly in examining the relation between changes in the IBDQ and changes in the activity of Crohn's disease, the IBDQ shows promise as a measure of health status for clinical trials in IBD.     

Increased expression of connective tissue growth factor in fibrotic human liver and in activated hepatic stellate cells

BACKGROUND/AIMS: Connective tissue growth factor is a recently described mitogenic protein implicated in a variety of fibrotic disorders. Connective tissue growth factor may be a downstream mediator of the pro-fibrotic and mitogenic actions of transforming growth factor-beta, promoting extracellular matrix deposition and fibrogenesis. As transforming growth factor-beta is considered important to the pathogenesis of hepatic fibrosis, we examined the possible contribution of connective tissue growth factor to this process. METHODS: Connective tissue growth factor expression was examined in normal and fibrotic human and rat livers using RT-PCR and ribonuclease protection assays, and in primary cultures of rat hepatic stellate cells by Northern and Western blotting. RESULTS: Ribonuclease protection assays demonstrated connective tissue growth factor mRNA was increased 3-5-fold in human fibrotic liver compared with normal. RT-PCR showed this mRNA was increased in carbon-tetrachloride-treated rat liver. Northern analysis showed connective tissue growth factor mRNA was increasingly expressed during progressive activation of cultured rat hepatic stellate cells. Western analysis confirmed that freshly isolated hepatic stellate cells secreted relatively little connective tissue growth factor compared with hepatic stellate cells activated in culture. Hepatic stellate cells stimulated with transforming growth factor-beta showed increased expression of connective tissue growth factor mRNA and protein. CONCLUSIONS: Connective tissue growth factor mRNA is consistently upregulated in human liver cirrhosis of various aetiologies, supporting a role for this growth factor in hepatic fibrogenesis. Our studies suggest that hepatic stellate cells may be an important source of hepatic connective tissue growth factor in vivo, particularly following stimulation with transforming growth factor-beta.     

Hospital preparedness for weapons of mass destruction incidents: an initial assessment.

STUDY OBJECTIVE: We performed an assessment of hospital preparedness for weapons of mass destruction (WMD) incidents in Federal Emergency Management Agency (FEMA) Region III. METHODS: Interviews of hospital personnel were completed in 30 hospitals. Data collected included level of preparedness, mass decontamination capabilities, training of hospital staff, and facility security capabilities. RESULTS: No respondents believed their sites were fully prepared to handle a biologic incident, 73% (22/30) believed they were not prepared to manage a chemical weapons incident, and 73% believed they were unprepared to handle a nuclear event. If a WMD incident were to occur, 73% of respondents stated a single-room decontamination process would be set up. Four (13%) hospitals (all rural) reported no decontamination plans. WMD preparedness had been incorporated into hospital disaster plans by 27% (8/30) of facilities. Eighty-seven percent (26/30) believed their emergency department could manage 10 to 50 casualties at once. Only 1 facility had stockpiled any medications for WMD treatment. All facilities had established networks of communication. No hospital had preprepared media statements specific to WMD. Nearly one fourth (7/30) stated that their hospital staff had some training in WMD event management. All reported need for WMD-specific training but identified obstacles to achieving this. Seventy-seven percent (23/30) of hospitals had a facility security plan in place, and half were able to perform a hospital-wide lock down. Ninety-six percent (29/30) reported no awareness regarding the threat of a secondary device. CONCLUSION: Hospitals in this sample do not appear to be prepared to handle WMD events, especially in areas such as mass decontamination, mass medical response, awareness among health care professionals, health communications, and facility security. Further research is warranted, including a detailed assessment of WMD preparedness using a statistically valid sample representative of hospital emergency personnel at the national level.     

Haemodynamic response to intravenous vasopressin and nitroglycerin in portal hypertension.

We have evaluated the haemodynamic effects of intravenous (iv) nitroglycerin (NG) and vasopressin (VP) alone and in combination, in 12 patients with cirrhosis and recent variceal haemorrhage (two to seven days). Nitroglycerin infusion alone (200 micrograms/min) produced a significant fall in portal pressure (WHVP-FHVP) (from 16.4 (0.6) to 13.3 (1.2) mmHg; p less than .001) associated with hypotension (mean arterial pressure from 95 (7) to 78 (9) mmHg; p less than 0.005). Vasopressin alone (0.4 IU/min) reduced portal pressure (20.7 (1.3) to 14.0 (1.3) mmHg; p less than 0.001), but there was considerable variation in the systemic haemodynamic changes with increased cardiac output in four of six patients. The combination of vasopressin and nitroglycerin corrected all systemic haemodynamic disturbances produced by either agent alone. This combination led, however, to a further reduction in portal pressure (from 13.7 (0.9) to 11.7 (0.7) mmHg p less than 0.01). These results show that: (1) intravenous nitroglycerin reduces portal pressure, and (2) the combination of nitroglycerin and vasopressin reverses systemic haemodynamic disturbances produced by either agent alone and leads to a further decrease in portal pressure.     

Coronary thrombosis postpartum in a young woman with Still's disease.

A young woman with Still's disease sustained a small myocardial infarction 12 weeks after the delivery of a healthy male infant. This pregnancy was complicated by late onset proteinuric hypertension. Coronary angiography nine days after infarction revealed intracoronary thrombus which had resolved by 3 months with antithrombotic therapy. The angiographic appearances at 3 months suggested that a local vasculitis may have been the precipitating cause.     

Clinical studies of advanced glycation end product inhibitors and diabetic kidney disease

Current treatment of the nephropathy complication of diabetes mellitus is suboptimal in halting the progression of the complex disease. Among the irreversible effects of sustained hyperglycemia is the heightened formation of advanced glycation end products (AGEs). The role of AGEs in diabetic nephropathy has been established by years of basic research. This article reports progression through human studies of the few AGE inhibitors that have reached clinical development, including pimagedine, pyridoxamine, and alagebrium.     

Effects of Deprivation and Pre-loading on the Experimental Consumption of Tea by Alcoholics and Social Drinkers

An analogy was drawn between the so-called compulsive behaviours af over-eating and over-drinking. A study of drinking by alcoholics and social drinkers (of a non-alcoholic drink) was based on the example of experiments which have analysed the differential effects of various environmental cues on over-eating. During repeated ‘tea taste’ sessions which alternated deprivation and preloading experimental conditions, a differential pattern of consumption was recorded from 14 hospitalised alcoholics and 14 normal drinkers from the local community. The normal drinkers drank significantly more of their overall tolal consumption when deprived (63 per cent) but the alcoholics drank similar quantities whether deprived (51·7 per cent), or preloaded (48·3 per cent).     

Anomalous origin of the left main pulmonary artery from the ascending aorta associated with Digeorge syndrome

We place on record 2 infants with the DiGeorge syndrome and anomalous origin of the left pulmonary artery from the ascending aorta. We postulate that: (1) embryogenesis of anomalous origin of the left pulmonary artery from the ascending aorta might be due to the persistent fifth aortic arch connecting both arterial systems; (2) an anomalous pulmonary artery arising from the ascending aorta is part of the aortic arch abnormality accompanied by normal conotruncal septation; and (3) in the DiGeorge syndrome, cardiac anomalies that originate from the conotruncus or aortic arch, or both, may have the same embryologic mechanisms.     

Quality of life in patients with inflammatory bowel disease

To investigate the effect of inflammatory bowel disease (IBD) on the quality of life, we interviewed 43 patients with ulcerative colitis (UC) and 54 with Crohn's disease. Patients identified frequent and important problems in five areas. Primary bowel symptoms, systemic symptoms, and altered emotional function were common; functional and social impairment were less frequent. Systemic symptoms such as fatigue were more prevalent in patients with Crohn's disease. Apart from primary bowel complaints, patients seldom volunteered other facets of quality of life impairment; this was particularly true for impairment of emotional function. We conclude that despite troublesome intestinal and systemic symptoms, most patients with IBD avoid major disruption in work and personal lives. Physicians must inquire specifically about emotional problems relating to IBD; in particular, fear of surgery is important to address. Psychosocial interventions should be targeted to those patients with problems in this area.