Elderly patients and chronic haemodialysis.
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Biomedical subjects
Publications and source records attributed to G J Krejs.
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Microalbuminuria is known to be associated with an increased risk for cardiovascular disease. It is detectable in acute myocardial infarction and could therefore also be a risk factor for reocclusion after percutaneous transluminal coronary angioplasty (PTCA). In our study follow-up coronary angiography was performed in 50 consecutive patients with a mean age of 56 years (38-70) on average 14 months after successful PTCA. Restenosis was defined as a decrease in diameter of 25% or more of the original result and one of at least 50% in vessel diameter. In the restenosis group there were 23 patients, and 27 showed no restenosis. The family history and anamnestic risk profile, results of the initially performed coronary angiography, and laboratory risk factors were comparable in the two groups. Median microalbumin was 11.2 mg/g creatinine in those with restenosis and 9.8 mg/g creatinine in those without. Using a cut-off of 10.0 mg/g creatinine, 12 of 23 patients with restenosis (52%) and 10 of 27 patients without (37%) were positive for microalbuminuria (NS). The incidence of microalbuminuria was higher in both groups compared to historical controls. Thus, in the restenosis group the incidence of microalbuminuria tended to be higher than in the nonrestenosis group, but since this difference did not reach statistical significance, it cannot be used to predict the risk of reocclusion after PTCA.
Although the adrenal glands are frequently the site of tumor metastases, adrenal insufficiency is exceedingly rare. We report on a patient with high-grade B-cell centroblastic lymphoma who initially presented with right axillary lymphadenopathy and bilateral adrenal masses. Four months after axillary lymphadenectomy the patient developed overt signs of Addison's disease. He recovered promptly after initiation of hormone replacement therapy and bilateral adrenalectomy. At present, 16 months after additional chemo- and radiation therapy the patient is considered free of tumor. To our knowledge this is the first report on a patient who presented with adrenal insufficiency in the course of non-Hodgkin's lymphoma and who was successfully treated. Demonstrating this case, we would also like to stress that the development of adrenal insufficiency does not necessarily indicate widespread tumor manifestation in patients with non-Hodgkin's lymphoma.
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In order to develop a model for secretory diarrhoea and to confirm the in vitro effects of cholera toxin in man in vivo the effect of intrajejunally administered cholera toxin was investigated in healthy volunteers. An intestinal perfusion technique with an occluding balloon proximal to the infusion site was used. The jejunum was perfused under steady state conditions with a plasma like electrolyte solution containing polyethylene glycol as a non-absorbable volume marker. After two control periods of one hour each, during which water was absorbed at a rate of 104 (14) (mean (SEM), n = 15) and 94 (15) ml/30 cm/h, respectively, three different doses of cholera toxin (6.25 micrograms, 12.5 micrograms, 25 micrograms) were administered by bolus into the lumen of the jejunum. Cholera toxin reduced absorption of water and electrolytes progressively over four hours and induced secretion in a dose dependent fashion. In the fourth hour net secretion amounted to 22 (23), 36 (24), and 88 (40) ml/30 cm/h (each n = five) with doses of 6.25, 12.5, and 25 micrograms cholera toxin, respectively. The movement of sodium, chloride, and bicarbonate paralleled water movement. Our results suggest that cholera toxin may serve as a secretory model in the human jejunum which might allow testing of new antisecretory agents.
Two abnormal hemoglobins were accidentally detected by cation exchange high performance liquid chromatography with the Diamat system of Bio-Rad Laboratories; the variants eluted together with the fast-moving Hb A1c. Structural analysis of isolated beta chains and sequence analysis of amplified DNA identified a new variant, i.e. Hb Graz that has a His-->Leu replacement at position 2 of the beta chain, in four healthy, apparently unrelated, adults. The second variant was identical to Hb Sherwood Forest or alpha 2 beta 2(104)(G6)Arg-->Thr; it is believed that this may be the second observation of this abnormal hemoglobin.
Six weeks after his return from a two-week vacation in Croatia a 52 year-old janitor from Graz complained of loss of appetite, fever, headache, and a 9-kg weight loss. The spleen was enlarged to 16cm as measured by sonography. Laboratory tests revealed pancytopenia, a prolonged prothrombin time and elevation of serum LDH concentration. While repeated bone marrow biopsy showed no signs of leishmaniasis, high antibody titers against leishmania antigen led to the diagnosis of kala-azar. The indirect immunofluorescent antibody test (1:128) and a haemagglutination-inhibition test (1:512) showed diagnostic elevations of titers. Therapy with pentostam led to prompt defervescence and resulted in a full recovery of the patient. After six weeks a marked decrease of antibody titers in the haemagglutination-inhibition test (1:16) could be observed. Leishmaniasis has to be considered in patients with fever of unknown origin who return from Mediterranean countries. Despite a negative bone marrow biopsy a diagnosis is possible on the basis of serological tests. This is important because effective therapy is available as illustrated by this patient and because of the fact that the disease runs a lethal course if the diagnosis is missed.
A 59 year old man presented with symptoms of partial bowel obstruction. Small bowel x-ray studies did not allow to identify the nature of the intestinal process in the upper ileum. At laparotomy small bowel encapsulation with a whitish membrane was encountered. Despite partial removal of this membrane small bowel obstruction persisted and two weeks postoperatively the patient died of peritonitis and cardiac insufficiency. Autopsy findings revealed massive fibrous adhesions in the abdomen with granulomatous inflammation. The presence of foreign body giant cells and bifringent crystals were characteristic for talcum powder. The latter suggested a causal role of an appendectomy 45 years earlier. The diagnosis of sclerosing encapsulating peritonitis as established in our patient needs to be separated from peritoneal encapsulation, a congenital malformation, and abdominal cocoon, which contains histological elements of inflammation. This case report should draw attention to these entities in the differential diagnosis and surgical management of small bowel obstruction.
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Neuropeptide Y is a neurotransmitter in enteric and postganglionic sympathetic neurons. In animal models of intestinal water and ion transport, neuropeptide Y decreases stimulated secretion but has no consistent effect on basal transport. In the present study, the effect of neuropeptide Y on jejunal water and electrolyte transport in healthy volunteers was investigated under basal conditions and during intestinal secretion induced by intraluminal administration of prostaglandin E2. The triple-lumen tube technique was used for perfusion of the small intestine with a plasmalike electrolyte solution containing polyethylene glycol as a nonabsorbable volume marker. After an initial control period (saline IV) neuropeptide Y was administered IV at a dose of 400 pmol.kg-1.h-1. Neuropeptide Y significantly increased net absorption of water, sodium, potassium, and chloride under basal conditions. The peptide significantly reduced the secretion of these electrolytes induced by an intraluminal prostaglandin E2 concentration of 5 mumol/L and reduced net water secretion by 36%. The results of the current study suggest that neuropeptide Y can change intestinal water and ion transport from secretion toward absorption.
In 14 severely anemic patients with end-stage renal disease and chronic hemodialysis the effect of recombinant human erythropoietin (EPO) on hemopoiesis was investigated. Bone marrow biopsies were taken before and after four and 26 months of treatment with EPO to evaluate quantitative and qualitative changes of histomorphology. EPO induced normalization of maturation and an increase in cell mass of the erythropoietic line in all patients. The number of megakaryocyte also increased significantly with EPO treatment (P less than 0.01). At the time of the third bone marrow biopsy (26 months) erythropoiesis was normal. Megakaryopoiesis remained unchanged compared to the second biopsy (4 months). No cytomorphologic abnormalities or other evidence for malignant disorder could be detected in any of the patients. Hematocrit increased from a mean of 19 to 31 percent at the second evaluation (P less than 0.001). Platelet count had risen by a mean of 30,000 at four months (P less than 0.05) and slightly decreased at 26 months. These observations suggest great safety of long-term treatment with recombinant human erythropoietin, and demonstrate efficacy in correcting reduced and immature erythropoiesis in chronically hemodialyzed patients. EPO also stimulates human megakaryopoiesis.
STUDY OBJECTIVE: The aim was to evaluate the effects of tissue concentration of amiodarone on ultrastructure and electrical activity in isolated spontaneously beating Langendorff perfused guinea pig hearts. DESIGN: Group 1: The influence of 10 microM amiodarone over a period of 1 h in a non-recirculated perfusate on conduction intervals, heart rate, creatine kinase concentration in the coronary effluent, coronary flow, and drug accumulation was determined. Group 2: Ultrastructural changes after 30 min and 60 min perfusion with amiodarone were examined. Group 3: Cardiac refractoriness was evaluated following 30 min and 60 min of perfusion with amiodarone. EXPERIMENTAL PREPARATIONS: Isolated hearts of guinea pigs (200-300 g) were used: group 1, n = 6 animals; group 2, n = 3 for each time span; and group 3, n = 6 for each time span. MEASUREMENTS AND MAIN RESULTS: A steady state for the effects of amiodarone on atrioventricular and intraventricular conduction [+31(SEM 5)%, p less than 0.01% +47(12)%, p less than 0.01, respectively] and on heart rate [-30(9)%, p less than 0.01] was reached after 15 min, and on His bundle conduction [+38(17)%, p less than 0.01] after 30 min. QT duration was not affected throughout the duration of the experiment. Cardiac refractoriness was significantly prolonged following 30 min perfusion with 10 microM amiodarone, and was further significantly increased following 60 min perfusion. Amiodarone tissue concentration increased to 365(39) nmol.g-1 wet weight, and this was accompanied by an increase in creatine kinase concentration in the coronary effluent. Coronary flow stayed constant throughout the whole experiment. At the end of the experiment electron microscopic examination of the myocardium of the left ventricle showed accumulation, fusion, and vacuolisation of mitochondria, and perinuclear oedema. CONCLUSIONS: These observations suggest that amiodarone, as well as exerting acute electrophysiological effects, creates ultrastructural changes which probably contribute to its effectiveness in arrhythmias caused by scarred myocardium.
Adverse hemorheologic effects induced by erythropoietin (EPO) treatment of renal anemia may pose a cerebrovascular risk. We therefore investigated the changes in cerebral perfusion, cerebral blood flow velocity (BFV) and neuropsychologic performance in 11 patients (mean age 37 years) receiving EPO. In response to EPO there was a significant (p less than 0.01) increase in hematocrit (35%), hemoglobin (43%) and whole-blood viscosity (50% at high and 90% at low shear rate). The initially increased blood flow velocity dropped significantly (p less than 0.05) and returned toward normal values in the middle cerebral arteries and the basilar artery (22 and 19% decrease, respectively). Global cerebral blood flow (CBF) decreased by 10% (not significant). The score of the Wechsler Adult Intelligence Scale digit symbol test improved significantly (p less than 0.01) after EPO treatment. None of the patients developed cerebrovascular symptoms or side effects. We conclude that the hematologic and rheologic changes following EPO treatment cause CBF and BFV to return toward normal and improve neuropsychologic performance in patients with end-stage renal disease.
In 167 patients with complete occlusion (greater than 3 cm) of the femoropopliteal artery, percutaneous transluminal laser angioplasty (PTLA) was performed after an unsuccessful attempt at crossing with a guide wire and was immediately followed by balloon dilatation. An Nd-YAG laser and an optical fiber delivery system with a sapphire tip serving as a contact probe were used for PTLA. In 132 of 167 (79%) patients, the occluded segment was successfully reopened. Clinical symptoms improved in 126 of 167 (75%) patients. PTLA was unsuccessful in 35 patients, and in 15 of these, injury of the vessel wall occurred. In one patient, surgical drainage of a large hematoma became necessary. All patients in whom recanalization had been achieved were randomized to receive long-term treatment with either phenprocumarol or acetylsalicylic acid (ASA) plus dipyridamole to prevent rethrombosis. At 36 months of follow-up, the cumulative patency rate (CPR) was 63%. A complete reobstruction in 32 patients (24%) and a partial reobstruction in 15 patients (11%) were found angiographically. The CPR after 36 months was significantly lower (p less than 0.05) in patients younger than 60 years of age (54%) than in patients older than 60 (68%); it was also significantly lower (p less than 0.05) in patients with reduced peripheral runoff (55%) due to obstructed arteries of the lower leg than in patients with unaffected runoff (73%). The CPR was 65% in recanalized segments shorter than 7 cm and was 62% in recanalized segments longer than 7 cm.(ABSTRACT TRUNCATED AT 250 WORDS)
Thirty patients with chronic non-A, non-B hepatitis (24 male, six female; median age 38 years, range: 15-68 years) were treated with recombinant interferon alfa-2b for 1 year. Treatment was started with 5 million units interferon alfa-2b daily for 2 weeks followed by 2 million units daily for another 2 weeks. Further doses were titrated according to alanine aminotransferase values. After 1 year, treatment was stopped and a follow-up biopsy was obtained. Thereafter, patients were followed for 6 months. Of the 24 patients who completed the 1-year treatment period, 14 (58%) had normal alanine aminotransferase values at the end of the study, eight of whom showed transient increases while on treatment. In another seven (29%), alanine aminotransferase levels decreased by more than 50% of pre-treatment values but remained above the normal range. Biopsies at the end of treatment showed a complete disappearance of inflammatory activity in four and a marked improvement in eleven other patients. The results of this study indicate that a 1-year treatment with recombinant interferon alfa-2b of patients with non-A, non-B hepatitis was very effective at normalizing or improving serum transaminases and liver histology. However, the overall relapse rate was 57%, with relapse occurring in a greater proportion of patients with temporary breakthroughs during therapy (requiring dosage increase), and particularly of patients with only a partial response to treatment (serum transaminases decreased by greater than or equal to 50%). Thus, further studies are needed to establish the optimal dose and duration of treatment to induce a complete resolution of the disease.
A strain of differentiated rat thyroid cells (FRTL5) in continuous culture was used to study the presence of thyroid growth-promoting immunoglobulins (TGI) in the serum of patients with endemic and sporadic euthyroid goiters. To identify true in vitro cell proliferation a microscopic mitotic arrest assay was used. Immunoglobulins G (IgGs) were prepared with QAE-Sephadex A-50 or protein-A-Sepharose. A positive growth stimulation index was found in IgG preparations of 65 of 71 patients with endemic goiter and in 9 of 14 IgG preparations of patients with sporadic goiter. IgG preparations of 15 control subjects from an area where endemic goiter due to iodine deficiency does not occur and of 18 subjects without iodine deficiency and without thyroid enlargement living in the endemic area did not stimulate FRTL5 cell growth. FRTL5 cell growth stimulation with IgGs of these euthyroid goiter patients could only be detected when IgG was tested in combination with a small dose of TSH. Immunoprecipitation with polyclonal and monoclonal antihuman IgG was able to abolish the growth-promoting effects. In 32 blinded samples the Feulgen cytobiochemical assay, formerly used to detect TGI, was compared with the FRTL5 mitotic arrest assay. The two methods showed similar results. Our observations of chromatographically purified IgG promoting thyroid cell proliferation in vitro provide good evidence that IgG was responsible for thyroid cell growth in vitro and suggest that autoimmune growth mechanisms may be involved in the pathogenesis of both endemic and sporadic goiters.
In this study a strain of differentiated rat thyroid cells in continuous culture was used to detect the presence of thyroid growth promoting immunoglobulins (TGI) in IgG preparations of serum of patients with endemic and sporadic euthyroid goiters. TGI was detected when FRTL5 cells were used in a mitotic arrest assay by costimulating the cells with IgG and a suboptimal dose of TSH. TGI was present in 65 of 71 endemic goter cases and in 9 of 14 sporadic goiter cases.
An 18-year-old male presented with Raynaud's phenomenon which was found to be caused by occlusion of the proper palmar digital arteries on the right hand and obstruction of the superficial palmar arterial arch on the left hand. These lesions in the arteries of both hands resemble those found in patients with vibration-induced white fingers such as in mine or foundry workers. The only likely cause for the pathological vascular findings in our patient was an exposure to vibration due to excessive off-street motorcycle driving. Therapy with intraarterial prostaglandins resolved the ischemic syndrome but it promptly recurred when the patient resumed motor cycle driving. Therefore, we suggest that excessive cross country motor cycle driving may cause vibration-induced white fingers.