Bioimpedance spectroscopy: a new tool to assess early esophageal changes linked to gastroesophageal reflux disease?

Bioimpedance spectroscopy can identify pathological changes related to precancerous lesions of the cervix uteri and esophagus. It therefore has the potential to detect early reflux-related changes in the esophageal mucosa, such as dilated intercellular spaces. The reliable detection of dilated intercellular spaces at the time of endoscopy would yield a significant diagnostic advantage for separating patients with functional heartburn from the large proportion of patients with gastroesophageal reflux symptoms but no macroscopic esophagitis or pathological acid exposure. The bioimpedance of the esophageal mucosa, measured with a small caliber probe, was evaluated in a series of preclinical experiments. First, sections of rabbit esophageal epithelium were mounted in Ussing chambers and exposed to solutions at pH 7.4 or pH 1.5 for 45 minutes. Impedance measurements were taken at varying probe pressures. Second, rabbit esophageal epithelia were perfused for 45 minutes in situ with pH 1.1 or control solutions and impedance measurements taken. Samples from both in vitro and in situ experiments were taken for morphological examination by light microscopy. Finally, esophageal bioimpedance was measured in awake dogs with permanent esophagocutaneous stoma. The in situ experiments demonstrated that morphological changes in the esophageal mucosa could be discerned by the use of bioimpedance spectroscopy. The variability in resistivity was species-independent but was affected by the pressure applied to the probe. The results suggest that evaluation of bioimpedance spectroscopy for use in a clinical setting is warranted. Small morphological differences in the esophageal mucosa may be detected by the use of bioimpedance spectroscopy.

Intravenous immunoglobulin prophylaxis causing liver damage in 16 of 77 patients with hypogammaglobulinemia or IgG subclass deficiency.

Sixteen of 77 patients (21 percent) with common variable immunodeficiency or IgG subclass deficiency contracted non-A, non-B hepatitis in association with intravenous infusions of immunoglobulin. The hepatitis seemed to run a more severe course in these patients than in non-immunodeficient patients. Twelve patients had clinical symptoms, and five died with hepatitis being the cause of death in two and a contributing factor in three. Liver biopsy specimens showed early chronic active hepatitis and cirrhosis. In addition to increases in liver enzymes, 13 patients had increases in alkaline phosphatase levels. All but two patients who contracted hepatitis had been given 50 mg/kg per week or more of intravenous immunoglobulin. Lymphocyte counts, T/B cell ratios, and T-lymphocyte function did not differ between those in whom hepatitis developed and those in whom it did not develop. The hepatitis was associated with more than one batch of a Swedish intravenous immunoglobulin, the immunoglobulin being derived from United States sources as well as from European plasma. Three previous brief reports in the literature have also associated non-A, non-B hepatitis with the intravenous infusion of various immunoglobulins. Biologic materials given to patients, including immunoglobulin, should, whenever possible, be prepared so as to ensure absence of viruses.

Evaluation of living renal donors. The current practice of US transplant centers.

To examine practice patterns regarding how living donors are evaluated and selected in the U.S., a survey was sent to all 231 United Network of Organ Sharing (UNOS)-approved transplant centers. Respondents from 75% of centers completed the questionnaire, all of whom utilize living donors for renal transplantation. Although the use of living-unrelated donors is also widely accepted (in 92% of centers), only 31% of responding centers performed such transplants in 1992, indicating a discrepancy between acceptance and actual practice. Morbidity (0.23%) and mortality (0.03%) of kidney donation continue to be low. The long-term risk of renal insufficiency in kidney donors appears to be similar to, or lower than, that in the general population. There is substantial variability in how potential donors are evaluated and what they are told regarding the risk involved in renal donation. There is also variability in exclusion criteria such as the acceptance of older donors (> 55 years old); those with borderline-to-mild hypertension, and those with borderline low glomerular filtration rate. Larger centers tended to be less rigid in their exclusion criteria compared with smaller centers. While our results indicate widespread acceptance and use of living donors, they also highlight the need for future studies to examine the efficacy of tests used in the evaluation process and to determine the long-term risks of renal donation.

Prognostic information from on-line vectorcardiography in acute myocardial infarction.

The present study assesses the prognostic information from continuous on-line vectorcardiography in patients with acute myocardial infarction (AMI). A series of 203 patients with AMI were studied. Vectorcardiographic (VCG) recordings were obtained continuously for 24 hours. Analysis was performed on-line with the commercial system MIDA CoroNet. QRS vector difference (QRS-VD), ST change vector magnitude (STC-VM), and ST vector magnitude (ST-VM) were monitored. Patients were followed for 538 +/- 220 days. During follow-up, 36 patients died from cardiac causes and 38 patients had reinfarction. A significantly higher occurrence of transient VCG changes (QRS-VD, STC-VM, and ST-VM; p < 0.001) was seen in patients who died from cardiac causes or experienced either cardiac death or reinfarction at follow-up. The end value for QRS-VD was higher in patients who died from cardiac causes and correlated with the maximal value for creatine kinase when all patients were considered (r = 0.66; p < 0.001). Significantly lower mortality was seen in patients with VCG trend curves suggestive of coronary reperfusion (p < 0.01). In multivariate analysis, occurrence of transient changes in STC-VM, high QRS-VD end value, and VCG trend curves not suggestive of reperfusion gave additional prognostic information beyond that of age, gender, maximal creatine kinase value, heart size on chest x-ray, occurrence of ventricular fibrillation during hospitalization, and the inability to perform exercise tests. VCG monitoring during the first 24 hours of hospitalization for an AMI is a promising method for early detection of patients with increased risk for subsequent cardiac death or reinfarction.

Effect of food on the pharmacokinetics of budesonide controlled ileal release capsules in patients with active Crohn's disease.

AIM: To study the influence of food on the systemic availability of budesonide in patients with active Crohn's disease. METHODS: Eight patients with an established diagnosis of Crohn's disease each received 9 mg budesonide controlled ileal release (CIR) capsules (Entocort capsules) orally on two separate occasions: once in a fasting state and once after a heavy breakfast. For reference, deuterium-labelled ((2)H(8)) budesonide, 0.5 mg, was given intravenously. Plasma concentrations of budesonide and (2)H(8)-budesonide were determined for 12 h, and their pharmacokinetic parameters were calculated. RESULTS: Average systemic availability of budesonide during fasting conditions was 10.7%, area under the curve was 27.5 nmol/L x h and peak plasma concentration was 4.1 nmol/L. Corresponding postprandial values were 13.2%, 27.0 nmol/L x h and 3. 8 nmol/L. Food increased the mean absorption time from 4.5 to 6.8 h (P=0.0012). Body clearance of budesonide was about 25% higher after eating (P=0.0015). CONCLUSIONS: Food had little influence on systemic availability and peak plasma concentrations of budesonide administered in CIR capsules. Absorption was retarded postprandially, likely due to delayed gastric emptying. Budesonide in CIR capsules can be administered at the same dose regardless of prandial status in patients with Crohn's disease.

A pharmacoscintigraphic evaluation of oral budesonide given as controlled-release (Entocort) capsules.

AIMS: To investigate the gastrointestinal pharmacokinetics of controlled-release (Entocort) and standard budesonide capsules. METHODS: Six Crohn's disease patients and eight healthy controls were given controlled-release capsules containing budesonide and an inert 111In label, following breakfast. In the patients, a standard capsule containing deuterium-labelled budesonide was given simultaneously. In the controls, on a separate occasion, the controlled-release capsules were given in the fasting state. Gastrointestinal transit was recorded by a gamma camera. Plasma budesonide and deuterium-labelled budesonide were used to estimate drug release, and urine cortisol was used to assess systemic effects. RESULTS: Budesonide delivery to the ileo-colonic region was significantly greater after the intake of the controlled-release capsules [69%; 95% confidence interval (CI), 54-84] than after the standard capsules (30%; 95% CI, 15-45) (P = 0.005). Fasting had little impact on uptake. The transit and pharmacokinetics of budesonide were similar in both subject groups, although systemic availability was higher in patients (21%; 95% CI, 13-33) than in controls (12%; 95% CI, 10-14) (P = 0.009). Urinary cortisol was, however, similar in both groups. CONCLUSIONS: A major fraction of budesonide is released in the ileum and throughout the colon, the intended target for the controlled-release formulation. The prandial state has little effect on budesonide uptake.

Pharmacokinetics of budesonide controlled ileal release capsules in children and adults with active Crohn's disease.

BACKGROUND: Systemic glucocorticosteroid therapy is effective in Crohn's disease, but is associated with side-effects. Budesonide has high topical anti-inflammatory activity, but considerably lower systemic activity than other oral glucocorticosteroids. AIM: To evaluate the systemic exposure to budesonide (controlled ileal release capsules) in children and adults with active Crohn's disease, and to assess the suppression of plasma cortisol. METHODS: In an open label study, patients (eight children and six adults) with active Crohn's disease received 9 mg budesonide (Entocort capsules) orally once daily for 7 days. Plasma concentrations were determined on the seventh day of administration, and pharmacokinetic parameters were calculated. For reference, 0.5 mg budesonide was given intravenously separately. Plasma cortisol levels were compared with the pre-treatment baseline values. RESULTS: Systemic exposure to budesonide (AUC0-24 h) after 1 week of oral administration was 41 +/- 21 nmol/L x h (mean +/- s.d.) in children and 35 +/- 20 nmol/L x h in adults. The estimated systemic availability in children was 9 +/- 5% and in adults 11 +/- 7%. The mean plasma cortisol (AUC0-24 h) decreased by 64 +/- 18% in children and by 50 +/- 27% in adults. CONCLUSIONS: The systemic exposure, systemic availability and cortisol suppression after oral administration of 9 mg budesonide were similar in children and adults with active Crohn's disease. Budesonide was well tolerated and no clinically important safety-related findings were identified.

Progression of hepatitis non-A, non-B to chronic active hepatitis: a histological follow-up of two cases.

Two patients with histologically verified acute hepatitis but without any serological evidence of hepatitis A or hepatitis B infection are described. In both cases the acute attack of hepatitis type 'non-A, non-B' progressed histologically and clinically to chronic active hepatitis within a two-year period. One of the patients died from liver insufficiency a year later, while the other is still alive after eight years of follow-up. The two cases illustrate that a progression of acute hepatitis 'non-A, non-B' to chronic liver disease may occur just as has been reported for hepatitis B infection.

Liver morphology in acute viral hepatitis related to the hepatitis B antigen.

The liver histology in infectious hepatitis or hepatitis A (HA) and serum hepatitis or hepatitis B (HB) is generally described as identical. However, the clinical separation of the two types has been a problem. Today a serological reaction based on the well documented association between hepatitis antigen and HB is of great assistance in the differential diagnosis. The present study of 165 hepatitis cases separated into hepatitis A and B by this test method indicates quantitative differences in the liver histology of the two types. Thus HB was associated with more prominent parenchymal cell damage and Kupffer cell reaction, while intrahepatic cholestasis was found in a significantly higher frequency in cases presumed to represent HA. The presence of intrahepatic cholestasis was associated with higher levels of serum bilirubin but otherwise no correlation was found between liver morphology and biochemical liver tests. The patients included a group of young intravenous amphetamine addicts with HB. No differences of importance were found histologically in addicts and other patients with hepatitis B.

Significance for the diagnosis of iron overload of histochemical and chemical iron in the liver of control subjects.

Storage iron was examined in surgical liver biopsy specimens in 43 haematologically normal and otherwise healthy adult individuals. These patients had no history of unphysiological iron losses nor of unphysiological iron intake. Histochemical iron was estimated in parenchymal and Kupffer cells and graded from 0 to 4+. Stainable iron of grade 1+ or more was present in parenchymal cells in 23 of the 27 men. Six of them had a 3+ grade. In nine cases iron was also visible in Kupffer cells. Visible iron was absent in most of the menstruating women. The mean total nonhaemin iron concentration for the male group was 80.2 (19.4 to 227.0), for the postmenopausal women 50.7 (19.3 to 106.6), and for the menstruating women 23.5 (5.5 to 65.9) mg./100 g. dry weight. The mean value for the women was significantly lower than the mean value for the men. There was a significant correlation between the histochemical grades of iron and chemically determined nonhaemin iron, but the degree of overlapping was considerable. The presence of stainable iron in the parenchymal liver cells is a normal finding. The significance of the present results with reference to familial studies of haemochromatosis is discussed.

Comparison of electrocardiograms recorded with standard leads and derived from the vectorcardiographic frank leads in high risk patients.

Dynamic vectorcardiography (VCG) is increasingly employed for ischaemia monitoring with the use of a computerized method for recording and on-line analysis by the calculation of trend parameters. To elucidate how well the derived electrocardiogram (dECG), calculated from the VCG, compares with the simultaneously registered standard ECG (sECG), dECGs from 17 postoperative cardiac-risk patients and 36 subjects with acute myocardial infarction (AMI) were compared to sECGs, both quantitatively in leads II, III, V2 and V5 and qualitatively. Despite small, but some significant differences, mainly in the amplitudes of precordial leads, the qualitative interpretation by two independent cardiologists showed good agreement between the methods (kappa = 0.72 and 0.67, respectively) for the diagnosis of AMI/ischaemia. The dECG seems to be reliable and can be used clinically in these groups of patients during VCG recordings.

Tumors of the thymus and thymic region: III. Clinicopathological studies on teratomas and tumors of Germ Cell type.

In a series of 82 patients with tumors of the thymus and thymic region there were 11 with teratomas and germinal tumors. Four of these patients had benign cystic teratomas, 4 had malignant teratomas, 1 had an embryonal carcinoma, and 2 had seminomas. The benign teratomas were removed by simple extirpation without complications. The malignant teratomas were highly invasive, and despite extensive operations and postoperative radiotherapy, 3 of the 4 patients died within 9 months. One patient with predominantly seminomatous differentation of the teratoma was alive and well more than 3 years after the operation. The patient with an embryonal carcinoma died after 4 months. One of the 2 patients with seminoma remained alive 20 years after radical excision and postoperative radiotherapy. The other, who had a huge seminoma, died during operation. The prognosis in patients with seminomas or with predominantly seminomatous structures in teratomas seems to be good after combined radical excision and radiotherapy, although nonradical resection followed by raditherapy may be justified in high-risk patients.

Tumors of the thymus and thymic region: I. Clinicopathological studies on thymomas.

A series of 43 patients with thymoma was reviewed. The patients were classified with respect to some factors of prognostic significance. The tumors were reclassified histologically, and a staging system with three defined stage-groups was applied to the series on the basis of operative findings and histological examination of surgical specimens. Surgical-pathological staging is of high prognostic and therapeutic importance in thymomas. Complete removal of the tumor was possible in the 25 patients with stage I or II disease and in 14 of the 18 patients with stage III tumors. Pleural metastases were observed in half of the patients with stage III disease. Even patients with extensive local spread or pleural metastases were subject to tumor resection. The treatment of choice is radical resection along in stage I; radical extirpation and, if indicated, postoperative radiotherapy in stage II; and radical resection whenever possible, even in cases of pleural spread, in stage III, with postoperative radiotherapy and chemotherapy. Myasthenia gravis is an indication rather than a contraindication to radical treatment of thymoma, although some patients may deterioratte. The importance of total thymectomy is stressed.

Tumors of the thymus and thymic region: II. Clinicopathological studies on Hodgkin's disease of the thymus.

Among 82 patients with a tumor in the thymic region, 17 had a lesion that fulfilled the criteria for Hodgkin's disease of the thymus; the histopathological differentiation of this entity from thymomas is discussed. All patients received surgical treatment and postoperative radiotherapy. After a mean observation time of 10 years there was no local recurrence and no death due to the disease, though 3 deaths were cuased by the treatment. New clinical manifestations occurred in 3 of the 14 long-term survivors: they were treated successfully by operation or irradiation. A very aggressive surgical approach involving extirpation of all tumor tissue, extensive excision of the surrounding tissues and adjacent lymph nodes, and supplementary radiotherapy seems to be the treatment of choice.

Macroprolactinomas: serial MR imaging in long-term bromocriptine therapy.

PURPOSE: To study the changes in macroprolactinomas during long-term bromocriptine therapy by means of serial MR imaging, and to correlate the findings to the serum prolactin (S-PRL) levels. PATIENTS AND METHODS: Thirteen patients with macroprolactinomas were studied before and during bromocriptine therapy; six to 11 MR examinations were performed with a duration of follow-up of 22 to 74 months. Tumor size, extension, relationship to adjacent structures, and signal intensity patterns were evaluated. Signal intensity ratios and T2 values were calculated in areas of apparently solid tumor tissue. RESULTS: Bromocriptine effectively reduced the size of all tumors; the size reduction was already significant at 1 week, but often continued for several years. Reenlargement during therapy was seen in three cases. The development of chiasmal herniation parallel to increasing cisternal invagination into the sella was a common finding, but was not correlated to visual symptoms. Signal intensity patterns corresponding to hemorrhage, cysts or necrosis were frequently observed, and transitions from one pattern to another were common. Hemorrhage occurred mainly in tumors corresponding to high initial serum prolactin levels. After 1 year of therapy, there was a significant increase in T2 values, indicating an increased water content in residual solid tumor tissue. CONCLUSIONS: MR is valuable for follow-up in bromocriptine therapy of macroprolactinomas, and provides new information on the tumor size changes, the inner structure of the tumors, and the optic chiasm.

Long-term octreotide therapy in growth hormone-secreting pituitary adenomas: evaluation with serial MR.

PURPOSE: To compare the changes in tumor volume with length of octreotide treatment in patients with acromegaly, to analyze signal alterations of the pituitary mass during treatment, and to determine an optimal MR imaging protocol. METHODS: Eighteen patients with growth hormone (GH)-secreting pituitary adenomas were studied with MR imaging before and during octreotide treatment. The length of follow-up was 9 to 70 months. Tumor volume, extension, and signal characteristics were evaluated. RESULTS: The total pituitary volume decreased in 16 patients by a mean of 37%. In 11 patients the tumor could be demarcated from the normal gland, and mean tumor reduction was 51%. Most of the tumor reduction took place within the first year, but an additional effect was noted in four patients during the following 3 years. Tumor reexpansion, hemorrhage, or necrosis did not occur. Serum GH levels were effectively lowered within the first year, with slight additional reductions thereafter. CONCLUSION: In long-term octreotide treatment of GH-secreting pituitary adenomas, tumor shrinkage occurs primarily during the first year, but effects are noted up to 4 years. The treatment may be considered an alternative to surgery in the select group of patients in whom the peripheral effects of chronic GH elevation, as determined by serum insulinlike growth factor I (IGF-I), are controlled. We suggest MR imaging with T1-weighted coronal and sagittal images at baseline and after 3 and 12 months, with additional MR imaging if GH or IGF-I levels rise during treatment. At baseline, both noncontrast and contrast-enhanced images should be obtained. Unenhanced images may be sufficient during follow-up unless tumor reexpansion occurs or surgery is anticipated.

Women react with more myocardial ischemia and angina pectoris during elective percutaneous transluminal coronary angioplasty.

BACKGROUND: Women have been considered to be at higher risk of complications relating to percutaneous transluminal coronary angioplasty (PTCA) than are men. One reason for this sex-related difference could be the ischemic response of myocardium during the procedure. OBJECTIVE: To investigate whether there are sex-related differences in ischemic response of myocardium during elective PTCA. METHODS: Consecutive patients (n = 192, of whom 48 were women), were subjected to vectorcardiography during the PTCA procedure. Vectorcardiographic variables, magnitude of ST-segment vector (ST-VM), and magnitude of ST-segment vector change (STC-VM) were studied. RESULTS: Women were older (63 +/- 10 versus 56 +/- 10 years, P< 0.001) than men in our study and more often had diabetes mellitus and hypertension. Women less often had stents implanted (24 versus 50%, P < 0.01) and they were subjected to fewer balloon inflations (P < 0.001), with a total inflation time shorter than that for men (P< 0.001). Maximum STC-VM was 25% greater for women (P < 0.05). Women reported greater maximum pain (P < 0.05) and nitroglycerine was more frequently used for them during PTCA (P < 0.05). Occurrence of episodes of residual ischemic STC-VM (the difference between total number of episodes and number of balloon inflations) was more common for women (3 +/- 5 versus 1 +/- 3, P< 0.01). Duration of residual ischemic STC-VM episodes (the difference between total duration of episodes and duration of balloon inflations) was longer for women than it was for men (242 +/- 275 versus 148 +/- 233 s, P < 0.05). In a stepwise multivariate analysis and for a matched case-control group, episodes of residual STC-VM and duration of residual STC-VM episodes still indicated that there was an independent sex-related difference (P < 0.01 and P < 0.01, respectively). CONCLUSIONS: Women more commonly develop vectorcardiographic signs of severe myocardial ischemia, more frequently experience episodes of ischemia and report more severe angina pectoris during elective PTCA than do men.

On-line vectorcardiography during elective coronary angioplasty indicates procedure-related myocardial infarction.

BACKGROUND: Increased creatine kinase concentrations after elective percutaneous transluminal coronary angioplasty (PTCA) have been shown to be associated with increased late cardiac mortality. OBJECTIVE: To evaluate the potential of continuous on-line vectorcardiography during elective PTCA to identify procedure-related myocardial infarction. METHODS: Patients (n = 192, ages 58 +/- 10 years), treated with elective and initially successful PTCA, were studied using vectorcardiogram (VCG) recordings. VCG monitoring was started 5 min before start of the PTCA and was carried out during the entire procedure, for at least 30 min after the first balloon inflation. ST-segment vector magnitude (ST-VM) and ST-segment change vector magnitude (STC-VM) were monitored. RESULTS: Fifteen (7.8%) procedure-related myocardial infarctions occurred. Indicators of procedure-related myocardial infarction were maximum value of ST-VM (P < 0.001) and STC-VM (P < 0.001), total ischemic time of all ST-VM episodes (P < 0.001) and STC-VM episodes (P < 0.001). The variable most closely related to a procedure-related myocardial infarction was the maximum STC-VM value during the procedure. With an optimized cutoff value, maximum STC-VM predicts a procedure-related myocardial infarction with a sensitivity of 93%, a specificity of 59% and a negative predictive value of 99%. Patients who had a stent implanted had significantly greater VCG values (P < 0.05-P < 0.001) than the group without a stent. There was a trend (P < 0.06) to a relation between increased creatine kinase concentration and stent implantation. In patients both with and without an implanted stent, greater STC-VM values were associated with procedure-related myocardial infarction (P < 0.01). CONCLUSION: Continuous VCG monitoring during elective PTCA is a promising method for immediate detection of patients at increased risk of procedure-related myocardial infarction.

Vascular access surgery for maintenance hemodialysis. Variables in hospital stay.

Access surgery in support of maintenance hemodialysis is a major factor contributing to prolonged hospitalization in the hemodialysis patient population. In surveying 140 consecutive patients admitted for access surgery, average length of stay was 14 days, independent of race or underlying cause of renal disease. Extended length of stay was most commonly encountered in older patients admitted for thrombosed fistulae or grafts. Postoperative fever, the need for repeated femoral catheterization, delay in access revision or placement due to infection, and the need for adequate social service support resulted in prolonged hospitalization. Understanding and preventing factors that prolong hospitalization may allow the minimization of length of stay in the future and improve quality of life for the end-stage renal disease patient, while also decreasing the cost of care.

The effect of steroids on the circulating lymphocyte population. II. Studies of the thoracic duct lymphocyte population of the guinea pig after neonatal thymectomy and prednisolone treatment.

The effect of corticosteroids on the lymphatic tissue and circulating lymphocyte pool in the guinea pig has been studied. No signs of increased lymphocytolysis was seen and only after 1--2 weeks treatment with a long acting corticosteroid was the thymic cortex reduced and thymic weight decreased. Three hours after injecting a short acting steroid a 30--40 per cent reduction in the thoracic duct cell count was seen in both control and thymectomized animals. Restitution to pretreatment cell level was completed in 17 hours. Mononuclear cells in the blood were markedly depressed up to 40 hours. The changes in the circulating lymphocyte pool in the resistant guinea pig seem to be in principle the same as in the sensitive rat but less pronounced. It can be concluded that the lymphocyte level in the circulating pool is thymus dependent but restoration of the cell count after steroid treatment is independent of intact thymic function. This data supports the hypothesis of lymphocyte trapping and redistribution after a single steroid treatment.