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Biomedical subjects

H Klein

Publications and source records attributed to H Klein.

At least 19 recordsLinked to original sources
PubMed1995

T lymphocyte-directed gene therapy for ADA- SCID: initial trial results after 4 years.

In 1990, a clinical trial was started using retroviral-mediated transfer of the adenosine deaminase (ADA) gene into the T cells of two children with severe combined immunodeficiency (ADA- SCID). The number of blood T cells normalized as did many cellular and humoral immune responses. Gene treatment ended after 2 years, but integrated vector and ADA gene expression in T cells persisted. Although many components remain to be perfected, it is concluded here that gene therapy can be a safe and effective addition to treatment for some patients with this severe immunodeficiency disease.

Adenosine Deaminase↗
PubMed1995

Effects of angiotensin II and phenylephrine on urinary endothelin in normal female volunteers.

Endothelin (ET) is a 21-amino acid peptide produced and secreted mainly by endothelial cells. Small amounts of ET are found in plasma, whereas large amounts are present in the urine. Despite the abundance of ET in the kidneys and urine, little is known about its regulation and clinical significance. The present study was designed to examine the effects of angiotensin II (Ang II) and phenylephrine (Phe) on the excretion of ET in normal female volunteers. Ang II and Phe were infused for 1 hour each and titrated to increase the mean arterial pressure by 20 mm Hg. There was a 60-minute recovery period before the second drug, and the order of the drugs was randomized. Infusion of Phe induced mild diuresis and natriuresis, which were associated with a significant increase in the excretion of ET. In addition, Phe significantly increased plasma atrial natriuretic factor (ANF). In contrast, infusion of equipressor doses of Ang II decreased urinary sodium excretion and did not significantly alter the excretion of ET. Moreover, Ang II induced only a small and nonsignificant increase in plasma ANF. These results demonstrate that (1) physiological doses of Ang II do not affect excretion of either ET or ANF; (2) Phe markedly increased the excretion of ET and ANF, independently of its effect on blood pressure; and (3) neither agent changed plasma ET, but Phe increased plasma ANF.

Adolescent↗
PubMed1995

Platelet membrane glycoproteins and microvesicles in blood from postoperative salvage: a study in cardiac bypass patients.

BACKGROUND: Transfusion of blood collected by intraoperative and postoperative salvage systems has been linked to the development of thrombocytopenia and disseminated intravascular coagulation. Although functional defects have been reported in platelets from unwashed salvaged blood, platelet membrane glycoprotein (GP) composition, a potentially important determinant of function and survival, has not been studied. STUDY DESIGN AND METHODS: Platelets from 22 patients whose blood was salvaged at the completion of surgery were analyzed and compared to platelets obtained from the venous blood from the same patient. Platelet membranes were stained with fluorescein isothiocyanate-conjugated CD41a monoclonal antibody (anti-GPIIb/IIIa) to identify platelets, a phycoerythrin-conjugated monoclonal antibody, CD62 (anti-P-selectin) to identify activated platelets, and CD42b (anti-GPIb) or anti-GPIb/IX to assess GPIb. Samples were analyzed with a flow cytometer using software. RESULTS: Platelets obtained from salvaged blood demonstrated lower GPIb expression (CD42b and GPIb/IX monoclonal antibody binding), higher P-selectin expression, and greater numbers of platelet-derived microvesicles. CONCLUSION: The clinical significance of transfusing blood containing activated platelets and microvesicles merits investigation.

Blood Platelets↗
PubMed1995

Infections after cardioverter-defibrillator implantation: observations in 335 patients over 10 years.

OBJECTIVE: To determine the incidence of infection after implantation of a cardioverter-defibrillator and the management of this complication. SUBJECTS: 335 consecutive patients who had a cardioverter-defibrillator implanted between January 1984 and December 1993. MAIN OUTCOME MEASURES: Incidence of infection within the first month after implantation (early infection) and after the first month (late infection). RESULTS: Infections associated with cardioverter-defibrillator devices occurred in 13 patients (3.9%) during a mean follow up of 22 (11) months. All patients had general signs of inflammation, fever (> 37.5 degrees C), and leucocytosis (> 10,000/ml) with or without purulent drainage. Five patients (38%) had infections during the first implantation, whereas eight patients (62%) had infections after replacement of the pulse generator. Early infection was observed in four patients (31%) and late infection in nine (69%). Incidence of infection was higher in patients who underwent epicardial cardioverter-defibrillator implantation (12/207 patients, 5.8%) than in those who received nonthoracotomy lead systems (1/125 patients, 0.8%) (P < 0.05). Infections were caused by staphyloccocus in 10 patients, pseudomonas in two patients, and streptococcus in one patient. The whole device had to be removed in all patients. During a mean follow up of 39 (29) months seven patients died: six of congestive heart failure and one of myocardial reinfarction. CONCLUSIONS: Infection, one of the most serious complications after cardioverter-defibrillator implantation, is associated with increased morbidity and mortality. When infection occurs the system must be removed to avoid a fatal outcome.

Adolescent↗
PubMed1995

Comparison of alendronate and sodium fluoride effects on cancellous and cortical bone in minipigs. A one-year study.

Fluoride stimulates trabecular bone formation, whereas bisphosphonates reduce bone resorption and turnover. Fracture prevention has not been convincingly demonstrated for either treatment so far. We compared the effects of 1-yr treatment of 9-mo-old minipigs with sodium fluoride (NaF, 2 mg/kg/d p.o.) or alendronate (ALN, 4 amino-1-hydroxybutylidene bisphosphonate monosodium, 1 mg/kg/d p.o.) on the biomechanical and histomorphometric properties of pig bones. As expected, NaF increased and ALN decreased bone turnover, but in these normal animals neither changed mean bone volume. NaF reduced the strength of cancellous bone from the L4 vertebra, relative to control animals, and the stiffness (resistance to deformation) of the femora, relative to the ALN group. In the ALN-treated animals, there was a strong positive correlation between bone strength and L5 cancellous bone volume, but no such correlation was observed in the NaF group. Furthermore, the modulus (resistance to deformation of the tissue) was inversely related to NaF content and there was a relative decrease in bone strength above 0.25 mg NaF/g bone. Moreover, within the range of changes measured in this study, there was an inverse correlation between bone turnover, estimated as the percentage of osteoid surface, and modulus. These findings have relevant implications regarding the use of these agents for osteoporosis therapy.

Alendronate↗
PubMed1995

[Treatment of ventricular tachycardia with bypass surgery. A case report].

We report on a 45-year-old man with a 4-year-old myocardial infarction and a history of recurrent syncopes. A monomorphic ventricular tachycardia was inducible during electrophysiologic study. After coronary bypass-grafting ventricular tachycardia was no longer inducible. The patient is now, 6 months after surgery, and without antiarrhythmic drugs, free from recurrence of syncope and has had no spontaneous tachycardia event. Treatment with antiarrhythmic drugs, endocardial resection, and the implantable cardioverter-defibrillator are well established approaches to fight sudden cardiac death. The role of coronary artery bypass-grafting alone in the prevention or suppression of malignant ventricular arrhythmias is debatable, especially in cases of monomorphic ventricular tachycardia. Some of these high-risk patients may well be protected by coronary artery bypass grafting alone.

Cardiac Pacing, Artificial↗
PubMed1995

[10 years of therapy with implantable defibrillators--observation in 353 patients].

Since January 1984, the cardioverter-defibrillator (ICD) has been implanted in 353 patients (pts). Epicardial ICD implantation was performed in 207 pts and 146 pts underwent non-thoracotomy ICD implant. Overall operative mortality was 3% (12/353 pts) and was significantly higher in pts with epicardial ICD implantation (11/207 pts, 5%) than in patients who received non-thoracotomy ICDs (1/146 pts, < 1%) (p < 0.05). During a mean follow-up of 25 +/- 23 months, 63 pts (19%) died: 8 pts (0.8% per year) from sudden arrhythmic death and 6 pts (0.8% per year) suddenly without an underlying arrhythmia. Cardiac death was observed in 36 pts (4% per year) and 13 pts (2% per year) died from other causes. Appropriate ICD discharges were observed in 245 pts (72%) with a mean incidence of 22 +/- 44 IC discharges per pt. In pts with third-generation ICDs, 3,542 ventricular tachyarrhythmias (VTA) were observed and terminated by primary ICD shocks in 778 VTA (22%). Antitachycardia pacing was attempted in 2,764 VTA (78%) and was successful in 2,484 VTA (90%).

Aged↗
PubMed1995

[The role of anti-tachycardia stimulation in patients with 3rd-generation defibrillators].

The most effective antitachycardia pacing mode (ATP) is still a matter of debate. Randomized prospective testing of 5 different ATP modes was performed in 82 patients (pts) prior to and after cardioverter defibrillator (ICD) implantation. The 5 ATP modes included 3-4 stimulation attempts with 4-10 adaptive scanning burst pulses. Adaptive burst coupling interval was 75% in mode A, 81% in mode B, 69% in mode C, 72% in mode D, and 88% in mode E. Auto-decremental scanning within bursts was 8 ms in modi A, B, and C, and 10 ms in modus E; autodecremental scanning between bursts was 8 ms in modi B and C, and 10 ms in modus D. During the pre-op electrophysiologic study (EP), termination (TR) of induced ventricular tachycardia (VT) was possible in 69% and by pre-discharge EP in 53%. Acceleration (AC) rates were 16% pre-op and 32% post-op (p = ns). There were no significant differences in TR or AC between modes A-E. During a mean follow-up of 18 +/- 4 (< 1-41) months, 3182 arrhythmia episodes (AE) occurred: 344 AE (11%) were terminated by primary ICD shocks and ATP was attempted in 2838 AE (89%) and was successful in 2576 AE (91%). AC occurred in 87 AE (3%) and ATP was without effect in 175 AE (6%). Our data show that ATP is helpful in patients with third-generation ICDs and is very effective during follow-up. However, there is no ideal ATP-mode visible in the present study.

Aged↗
PubMed1994

The tripartite DNA element responsible for diet-induced rat fatty acid synthase (FAS) regulation.

We investigated which region of the 5'-flanking sequence of the rat fatty acid synthase (FAS)-encoding gene could be responsible for its nutritionally regulated expression. Diet-induced differences in chromatin structure were determined by DNase I treatment of intact nuclei from hepatic tissue. A low-fat diet results in a different pattern of DNase I-hypersensitive sites (HS) in the chromatin of the FAS promoter (pFAS) from that seen when the nuclear extract was prepared from the livers of normally fed rats. The protein-binding properties of the region defined by DNase I hypersensitivity were tested by gel retardation. A putative cis-acting element with a tripartite structure, 5'-GCCT, 6-bp spacer and a 3'-palindrome, could be localized between bp -518 to -495 in pFAS. Competition experiments with oligodeoxyribonucleotides (oligos) representing subfragments of this cis-element showed that the requirement for structure is stricter than that for sequence. This element could be one of the termini of the insulin-induced signal cascade.

Animals↗
PubMed1994

Pleomorphic pineocytoma with extensive neuronal differentiation: report of two cases.

Two pineal parenchymal tumors are presented, arising in a 54-year-old man and a 72-year-old woman; respectively. They showed isomorphic, cellular areas of small cells, often with characteristic pineocytomatous rosettes, and of medium-sized cells, as well as less cellular regions with highly pleomorphic, often ganglioid large cells. Immunohistochemistry disclosed extensive neuronal differentiation. There was intense positivity for neurofilament protein and microtubule-associated protein 2 in the pleomorphic areas and more variable expression in the isomorphic regions. Diffuse synaptophysin positivity was seen, accentuated along the borders of pleomorphic cells and in the rosettes, as well as diffuse interstitial and/or cytoplasmic expression of neuron-specific enolase, PGP 9.5 and tau. beta-Tubulin III was detected in most cells and slight positivity was found in the rosettes. Expression of glial fibrillary acidic protein, however, was restricted to resident astrocytes and an interstitial network of processes. These neuronally differentiated pleomorphic pineocytomas underline the broad histomorphological spectrum of pineal parenchymal tumors.

Aged↗
PubMed1994

Risk and benefit of additional aortocoronary bypass grafting in patients undergoing cardioverter-defibrillator implantation.

It is unclear whether additional aortocoronary bypass grafting should be performed in patients who need an automatic implantable cardioverter defibrillator (ICD) in one- or two-step procedures. Therefore we studied the follow-up of 139 patients who underwent epicardial implantation of the cardioverter defibrillator (CD). All patients had coronary artery disease and recurrent ventricular tachycardia or fibrillation. Eighty-nine patients had implantation of the CD without additional surgical approaches (group G1), and 50 patients had concomitant aortocoronary bypass grafting (group G2). Perioperative mortality (within 30 days after CD implant) was 1 (1%) of 89 patients in G1 and 6 (12%) of 50 patients in G2 (p < 0.01). During the mean follow-up of 26 +/- 20 months, sudden death occurred in four (4%) of 89 patients in G1 and two (4%) of 50 patients in G2. Twenty-three (17%) patients died of cardiac failure (18 [20%] patients in G1 and 5 [10%] patients in G2). ICD discharges occurred in 69 (78%) of 89 patients in G1 and in 36 (72%) of 50 patients in G2. The mean incidence of ICD discharges was 23 +/- 69 shocks per patient in G1 and 18 +/- 25 shocks per patient in G2 (p = NS). We conclude that concomitant aortocoronary bypass grafting during CD implantation leads to a higher perioperative mortality. Avoidance of myocardial ischemia does not significantly influence sudden death mortality nor markedly reduce the number of ICD discharges.

Adult↗
PubMed1994

In-111 monoclonal antibody versus Ga-67 citrate and Tc-99m SC subtraction in a patient with malignant melanoma.

Gallium-67 is routinely used for follow-up of patients with malignant melanoma. However, its nonspecificity for melanoma and its high rate of false-positive results have always been a matter of concern. The authors describe a patient who encountered serious problems with the use of gallium. Because gallium is taken up well by the liver and by melanoma, results of gallium scintigraphy of the liver may appear normal even if there is metastatic disease. In this patient, results of gallium scintigraphy of the liver were negative for metastasis but revealed extrahepatic foci detected by the monoclonal antibody. Computed tomography showed areas of attenuation, revealing only a few intrahepatic tumors and no extrahepatic disease. Tc-99m SC revealed intrahepatic metastases, but no extra-hepatic metastases were seen. A monoclonal antibody (ZME-018) scintigram did reveal hepatic metastases along with probable small, extrahepatic, metastatic foci. Overall hepatic uptake of the monoclonal antibody was relatively low. An image subtraction algorithm was devised whereby the sulfur colloid image was subtracted from the gallium scintigram. The resultant image revealed both the intrahepatic and extrahepatic metastases seen on the ZME-018 images. It is likely that in the past many hepatic metastases have been missed because Tc-99m SC images have not been routinely used as part of melanoma management protocols. The uptake of the ZME-018 by the tumor was significantly higher than that of the normal liver, suggesting that ZME-018 labeled with the appropriate emitter may be an effective specific therapeutic tool in selected patients.

Adult↗
PubMed1994

Role of antitachycardia pacing in patients with third generation cardioverter defibrillators.

The most effective antitachycardia pacing (ATP) mode is still a matter of debate. Randomized prospective testing of 3 different ATP modes was performed in 65 patients (pts) prior to and after cardioverter defibrillator implantation (Ventak PRx 36 pts, Cadence V 100 29 pts). All 3 ATP modes included 4 stimulation attempts with 4-7 adaptive scanning burst pulses. Adaptive burst coupling interval was 75% in mode A, 81% in mode B and 69% in mode C. Autodecremental scanning within bursts was 8 msec in all, decremental scanning between bursts was 8 msec in modes B and C. Each ATP mode had to be tested 3 times; all 3 ATP modes were randomly applied to each pt. During preoperative testing 91 of 133 VT episodes (68%) could be terminated by ATP. Termination was achieved in 68% with mode A, 68% with mode B and 73% with mode C. During predischarge testing, 251 VTs were induced and ATP was successful in 147 VTs (59%). Termination rate was 56% with mode A, 68% with mode B and 50% with mode C. During the mean follow-up of 12 months, 2301 arrhythmia episodes (AE) occurred. ATP was performed in 2097 AE (91%) and successful in 1920 AE (92%). Acceleration of VT occurred in 65 AE (3%) and unsuccessful ATP was observed in 112 AE (5%). It is concluded that ATP in general is highly effective in pts with sustained VT. None of the tested ATP modes, however, proved to be superior to the other.

Aged↗
PubMed1994

Nonpharmacological therapy of ventricular tachyarrhythmias: observations in 554 patients.

It has been shown that conventional antiarrhythmic drug treatment is debatable, and there is growing interest in nonpharmacological techniques. We studied the outcome of 554 patients with ventricular tachycardia (VT) or ventricular fibrillation (VF) who underwent nonpharmacological techniques from March 1980 to June 1994 at our institution. Catheter ablation was performed in 51 patients (G1), map guided surgery in 147 (G2), and cardioverter defibrillator implantation (ICD) in 356 (G3). During a mean follow-up of 37 +/- 12 (< 1-137) months, incidence of sudden death (G1 4%, G2 6%, G3 3%) and cardiac death (G1 7%, G2 16%, G3 8%) were relatively low, and there was no significant differences between G1-G3. VT/VF recurrences occurred more frequently in G1 (57%) than in G2 (18%) (P < 0.01). ICD discharges occurred in 69% of patients. We conclude that nonpharmacological techniques lead to low sudden death rates; however, there is a high rate of recurrence in G1. Risk stratification is necessary to select the ideal therapy for each individual patient.

Catheter Ablation↗
PubMed1994

Atrial natriuretic peptide and dopamine in a dog model of acute renal ischemia.

Atrial natriuretic peptide (ANP) has been shown to reverse functional impairment in ischemic acute renal failure (ARF). To prolong and/or to enhance the effects of peptide, in this investigation dopamine (D) (3 micrograms/kg BW/min) was applied together with ANP (100 ng/kg BW/min) after 90 min unilateral renal artery occlusion in anesthetized dogs. ANP significantly increased creatine clearance, filtration fraction, diuresis, sodium excretion, sodium reabsorption, and free water clearance, as in postinfusion period only V remained elevated. D alone did not effect renal function beneficially. ANP+D improved kidney function impairment to a level comparable with that of ANP alone, but V and UNa.V remained increased in the postinfusion period. MAP was elevated during ANP+D infusion as compared to ANP alone and was sustained to the end of the experiment. We conclude that D does not potentiate the positive effects of ANP on postischemic kidney, but prolongs its action on UNa.V, possibly by maintenance of high MAP after renal ischemia.

Acute Kidney Injury↗