Unproven therapies in the treatment of cancer.
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Biomedical subjects
Publications and source records attributed to R Bloch.
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A compact, absolutely stable numerical method is presented to integrate stiff systems of pseudo-linear, ordinary, first-order differential equations, commonly found in the simulation of biological models. Solutions are stepwise approximated by a complete set of first order rational polynomials. Mass balance is preserved by the approximations. No matrix inversions are required. Besides being stable, the method is also convergent and can be used with deferred approximation to the limit h = 0. Comparisons between this method and the Stoer-Bullirsch algorithm and fourth-order Runge-Kutta method are presented.
To determine whether multiple carriers are responsible for luminal uptake of glycyl-L-proline (Gly-Pro) in the renal proximal tubule, transport of Gly-[3H]Pro was measured in brush-border membrane vesicles (BBMV). A Line-weaver-Burk analysis of Michaelis-Menten kinetics revealed the presence of two carriers: a lower affinity, higher capacity carrier (Km = 1.3 x 10(-2) M; Vmax = 4.6 x 10(-8) mol.mg-1.min-1) and a higher affinity, lower capacity carrier (Km = 2.7 x 10(-7) M; Vmax = 7.8 x 10(-13) mol.mg-1.min-1). The dipeptides Gly-Sar, beta Ala-His, and pyroGlu-His competitively inhibited the low-affinity carrier. No effect on the Km or Vmax of Gly-Pro transport in this range was seen in the presence of the dipeptides Gly-Gly or cycloHis-Pro. The high-affinity carrier exhibited a different inhibition spectrum. Competitive inhibition of Gly-Pro transport was demonstrated for the dipeptides Gly-Gly and Gly-Sar. However, none of the other peptides tested above altered Gly-Pro transport in the high-affinity range, including pyroGlu-His, which is transported by a high-affinity carrier. At both low (4 x 10(-8) M) and high (4 x 10(-3) M) concentrations, uptake of Gly-Pro was stimulated in the presence of an inwardly directed H+ gradient but was unaffected by the presence of an inward Na+ gradient. In addition, measurements in the presence of valinomycin and an outwardly directed K+ gradient strongly suggest that H(+)-stimulated uptake at both concentrations is electrogenic.(ABSTRACT TRUNCATED AT 250 WORDS)
This study investigated 238 consecutive admissions to an adult head trauma unit during six years. Eighty-seven patients with posttraumatic epilepsy (PTE) were identified. Rehabilitation outcome was measured by a locally developed rating scale obtained at admission and discharge for all head trauma patients. The PTE and non-PTE groups were comparable in terms of demographic and medical characteristics except for proportion of men, which was higher in the PTE group (84% vs 66%, p less than .05). Both groups demonstrated significant functional gains on all measures during the course of their hospitalization (p less than .01), although the PTE patients demonstrated lower levels of function at admission and discharge on items rated by physical, occupational, speech, and recreation therapists, and by psychologists. Furthermore, PTE patients required a higher level of nursing care on discharge (p less than .05). It appears that PTE does not impede the rehabilitation process but significantly impacts posthospital rehabilitation plans of patients with blunt head injuries.
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These studies were performed to determine if a transmembrane carrier for pyroglutamyl-histidine (pGlu-His) is present in the luminal membrane of renal proximal tubular cells. Previous studies have suggested the intact transepithelial transport of pGlu-His, a dipeptide formed by the hydrolysis of luteinizing hormone-releasing hormone by enzymes associated with the brush border in the proximal nephron. With the use of a renal brush border membrane vesicle preparation, pGlu-His showed H+-stimulated, Na-independent, saturable transport into an osmotically active space. High-pressure liquid chromatographic analysis of both the intravesicular and extravesicular fluids indicated intact uptake of the dipeptide. The transport constant (Kt) and Vmax for pGlu-His transport were 9.3 X 10(-8) M and 6.1 X 10(-12) mol.mg-1.min-1, respectively. Transport of pGlu-His was not inhibited by the dipeptides glycyl-proline, glycyl-sarcosine, and N-beta-alanyl-L-histidine, which have been previously shown to be transported into renal brush border vesicles via a single, low-affinity, high-capacity, Na-independent, and H+-stimulated peptide carrier. In addition, the gamma-glutamyl-containing peptides gamma-glutamyl-histidine and N(N-L-gamma-glutamyl-L-cysteinyl)glycine and the tripeptide pyroglutamyl-histidyl-prolinamide were without an inhibitory effect. In contrast, transport of pGlu-His was inhibited by the dipeptide pyroglutamyl-alanine. This study demonstrates the existence of a high-affinity, low-capacity H+ cotransport system for pGlu-His in the proximal tubular luminal plasmalemma, which appears to be specific for pyroglutamyl-containing dipeptides. The data indicate that multiple dipeptide carriers are present in the proximal nephron.
Stress relaxation experiments were performed on specimens from a human intervertebral disc. Specimens were made from the nucleus pulposus and from the external lamellae of the anulus fibrosus in two different orientations. Tests were run with varying moisture content so as to develop a relaxation master curve. A model was developed based on the experimental data. It was found that the short term master curve for the lamellae of the anulus and nucleus are similar, whereas the long term rubbery plateau is different between the lamellae and the nucleus. It was also established that the master curves for different lamellae and the nucleus were shifted relative to each other in the time domain due to changes in water content. The average relaxation modulus of the whole disc was obtained by averaging the properties between the anulus and nucleus. This model was then used for studies of Schmorl's nodes, of degenerated discs and for circumstances in which hydration is considered to be important.
Criteria are presented to assist in the critical appraisal of investigations into the efficacy of therapy for low-back pain. Potential sources of statistical noise and experimental bias are identified in the selection of subjects, the application of therapy, and the evaluation of outcomes. When these criteria were applied to a series of recent articles, published in this journal, only two valid randomized controlled trials and four properly controlled cohort studies were found out of 147 reports.
Water content of intervertebral discs is a significant aspect of both viscoelastic behavior and age-related degenerative changes. Using water content as a dependent variable, stress-relaxation was measured using standardized anulus fibrosus specimens strained at various levels of strain. Synthesis of experimental data into a master relaxation curve allows prediction of specimen response over time intervals not readily accessible experimentally. A quantitative understanding of the role of water content may have important clinical application, since magnetic resonance imaging is a tool which should allow water content determination in vivo.
The case of a 32-year old man with exocrine pancreatic insufficiency and progressive weight loss is reported. Ultrasound examination of the abdomen revealed a huge tumor of the pancreatic head. Smears obtained by a percutaneous fine-needle biopsy showed characteristics of a neuroendocrine tumor. Serum hormone levels and immunocytochemistry presented no evidence for a hormonal activity of the tumor. The exocrine pancreatic insufficiency was explained by an obstruction of the pancreatic duct system. In the present case report the problems of diagnostic approaches to endocrine pancreatic tumors are discussed.
Microaspiration techniques and clearance studies have shown that reabsorption of filtered sodium approximates 65% in the proximal tubule, 25 to 30% in the ascending limb of the loop of Henle and 5 to 10% in the dilution segment. Reabsorption in the Henle loop is of special significance as it governs the process of dilution-concentration of urine. Moreover, inhibition of sodium reabsorption in the loop of Henle necessarily produces a substantial loss of sodium since only a fairly small fraction of urinary sodium is reabsorbed beyond the Henle loop (dilution segment, distal tubule). Excretion of water and electrolytes is regulated by humoral factors, such as the renin-angiotensin-aldosterone system, some prostaglandins and certain kinins. Factors that promote excretion of sodium, produced in particular by the myocardium, have recently been demonstrated. The correlation between blood pressure and salt has been substantiated by many findings. Diuretics are commonly used to treat high blood pressure as well as edema. Recent evidence indicates that sodium transport is altered in idiopathic hypertension, at least in red blood cells. Clinical trials of diuretics are designed to localize the drug's action and quantify its saluretic activity (evaluation of potency and effectiveness--single doses, sustained treatment). Furthermore, the minimal efficient antihypertensive dosage should be determined. Diuretics can be divided into two groups according to whether they produce an increase or decrease in serum potassium. Diuretics that are capable of producing hypokalemia belong to two main families. One consists of the Henle loop diuretics that interfere with the mechanisms of dilution-concentration of urine. Action of these drugs is potent and short-lived. For instance, following a single dose of furosemide, excretion of sodium can reach 25-30% of filtered sodium; renal blood flow increases; CH2O and TCH2O decrease. With furosemide, induction of diuresis is rapid (within a few minutes after IV injection and 20 mn after oral ingestion); elimination half-life is 50 mn; absolute bioavailability is 50-70%; 95% of the drug is bound to plasma proteins; elimination is mainly through the kidneys. Other Henle loop diuretics include ethacrynic acid, whose elimination half-life is less than one hour; bumetanide, which is 40 times more potent than furosemide; muzolimine, whose action is more lasting despite the fact that only 65% of the drug is bound to plasma proteins; and ozolinone, which has a saliuretic action comparable to that of furosemide and in addition exerts a direct vasodilating effect.(ABSTRACT TRUNCATED AT 400 WORDS)
Cardiovascular and humoral responses to extremes of sodium intake (10-1500 mEq/day) were studied. Chest radiographs of eight normal men were obtained to measure changes in heart volume and central vascular structures. Echocardiographic measurements of cardiac chamber dimensions were also obtained. Sodium loading resulted in a 16-mm-Hg increase in mean arterial pressure and increases in cardiac output, stroke volume, left ventricular end-diastolic volume, and all radiographically determined cardiac dimensions. There was direct correlation between the radiographic cardiac dimensions and left ventricular end-diastolic volume. There was no echocardiographic evidence of pericardial fluid. After sodium loading, there was enlargement of the superior vena cava, innominate veins, azygos vein, pulmonary vessels, and the aortic knob. Small pleural effusions were commonly seen. Volume expansion may cause radiographic changes that may mimic those associated with congestive heart failure. This may particularly be the case in patients with renal failure, those receiving dialysis treatment, or patients receiving large volumes of intravenous fluids.
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Extensive follow-up investigations were done in 1978 in 135 patients, most of whom had been operated for colo-rectal carcinoma of all stages in 1977. In 71% of the cases no or no sufficient postoperative control had been performed in the patients' own area. At the follow-up investigations 11 recurrences in the anastomosis, 10 of which were operable, 20 distant metastases, 1 simultaneous second carcinoma, 15 adenomas, partially with numerous atypical cells, 1 polyposis coli and 23 nonspecific granulomas of the anastomosis were detected. The Haemoccult test was positive in 3 of the 11 anastomotic recurrences. Only in cases of distant metastases were values of carcinoembryonic antigen clearly increased (greater than 5 ng/ml). These findings underline the necessity of intensifying the regular follow-up investigation in colo-rectal carcinoma.
We have examined the rate of degradation of the total acetylcholine receptor content of diaphragm muscles of young rats and have found that even in muscles from 1-day-old rats some receptors are metabolically more stable than adult extrajunctional receptors. Further experiments have shown that acetylcholine receptors at junctional regions from young rats are degraded slowly, whereas those in extrajunctional regions are degraded rapidly. The results demonstrate that junctional acetylcholine receptors in rat diaphragm are degraded at a slow rate characteristic of adult junctional receptors at all ages after birth.