Search PubMed⌕ Search

Biomedical subjects

A Zimmermann

Publications and source records attributed to A Zimmermann.

At least 289 records · Page 16Linked to original sources
PubMed1989

Resectability of large focal liver lesions.

Despite modern imaging techniques evaluation of the resectability of large focal liver lesions is often difficult or impossible until the time of operation. Based on experience with 54 primary or secondary focal liver tumours, a simple morphological classification has been found to be reasonably predictive of resectability. All tumours were classified before operation using computed tomography, ultrasound and angiography; 38 patients underwent laparotomy. Dependent, 'hanging' tumours (n = 7) were resected in six cases, expansively growing 'pushing' tumours (n = 19) were resected in 18 cases, and infiltrating, 'invasive' tumours (n = 17) were not resected because of involvement with major vascular structures. Eleven small tumours (less than 5 cm) were not classifiable by this system. This simple classification may be a useful clinical concept in preoperative assessment of resectability of focal liver lesions. Hanging tumours should always be resected, and large expansile tumours are generally resectable despite their size. Invasive tumours can only be resected in exceptional cases.

Humans↗
PubMed1989

Study of acute renal ischemia in the rat using magnetic resonance imaging and spectroscopy.

Magnetic resonance (MR) imaging and spectroscopy, chemical lactate measurements, and microscopic examinations were performed to investigate acute renal ischemia in rats. MR images (1H) and spectra (31P and 1H) were acquired on a 2.0-T superconducting small-bore magnet by using implanted coils. Occlusion of the renal artery induced a significant decrease in signal intensity of the renal parenchyma on T2-weighted images, which was most obvious in the outer medulla (-50 +/- 15%, n = 8, P less than 0.001) and was the result of venous congestion, as verified histologically, 31P spectroscopy demonstrated a drop in pH from 7.3 +/- 0.2 to 6.6 +/- 0.2 (n = 18, P less than 0.001), characterized by a time constant (Tc) in the same range as that of the depletion of ATP (2.3 +/- 1.3 min versus 1.9 +/- 1.2 min, n = 10, P = ns). By means of 1H spectroscopy, a lactate peak was detected within 1.5 to 4 min of ischemia, still increasing in intensity after 1 h of ischemia. The Tc of the lactate buildup (15.9 +/- 7.5 min, n = 8) was significantly longer than that of the drop in pH (P less than 0.005). The chemically measured intrarenal concentration of lactate was 1.3 +/- 0.5 mumol/g in control kidneys and 8.7 +/- 3.2 mumol/g (P less than 0.005) in kidneys made ischemic for 1 h. The present study demonstrated important features of acute renal ischemia: (a) acute ischemia induces venous congestion in the medulla; (b) accumulation of lactate is not the main cause of the intracellular acidification observed during ischemia.

Animals↗
PubMed1989

Effect of secretin on bile formation in rats with cirrhosis of the liver: structure-function relationship.

To investigate whether the hypercholeresis seen in cirrhotic humans and animals is due to ductular proliferation or altered inactivation of secretin, or both, we studied the response of bile flow and biliary erythritol clearance to synthetic porcine secretin in rats rendered cirrhotic by chronic exposure to phenobarbital/carbon tetrachloride (n = 11) and untreated control rats (n = 5). Bile duct mass was determined morphometrically. Furthermore, plasma disappearance of secretin was measured by radioimmunoassay. Basal bile flow did not differ between the two groups. Whereas secretin had no effect in the control group, it stimulated bile flow by 49% +/- 33% in the cirrhotic group (p less than 0.001). Erythritol bile-to-plasma ratio was lower and biliary bicarbonate concentration higher in the cirrhotic rats, suggesting some ductular contribution to bile flow even in the absence of secretin. Biliary bicarbonate concentration did not increase further during secretin administration, whereas bile salt concentration decreased from 27 +/- 6 to 18 +/- 4 mM. The elimination half-life of secretin was not affected by cirrhosis, averaging 5 +/- 2 min in both groups. Bile duct volume was increased in cirrhotics (2.9% +/- 1.4% vs. 0.2% +/- 0.1%; p less than 0.01) and showed an excellent correlation with the maximal secretin-induced increment of bile flow. Our results suggest that the proliferating ductules contribute to bile flow and that increased secretin responsiveness is not due to altered pharmacokinetics in cirrhotic rat liver.

Animals↗
PubMed1989

Dynamic pion irradiation of unresectable soft tissue sarcomas.

Since November 1981, when pion irradiation was introduced for deep seated tumors at the Swiss Institute for Nuclear Research (SIN, now Paul Scherrer Institute, PSI) a dynamic, 3-dimensional spot scan treatment technique has been in use. To exploit this technique a special optimization treatment planning system has been designed. Of a total of 331 patients treated with pions from November 1981-December 1987, 35 were irradiated for unresectable soft tissue sarcomas. In 32/35 patients, tumor sites were retroperitoneal, pelvic or in the groin or thigh. Twenty-nine tumors had a maximum diameter of greater than 10 cm, 18 tumors of greater than 15 cm; 30 tumors had grade 2/3 and 32 Stage III B/IV A/IV B. Eight of 35 patients received a low pion total dose, 7-27 Gy. Twenty-seven patients received a total dose of 30-36 Gy, fraction size 150-170 cGy (90%-isodose), 20 fractions, 4 times per week. Of these 27 patients, severe late reactions appeared in five: 2/8 patients with extremity/groin sarcomas (1/2 caused by biopsy) and 3/19 patients with retroperitoneal/pelvic sarcomas (one a skin reaction after Actinomycin-D, one a small bowel reaction after 36 Gy, a dose no longer used). Seven of 27 patients had metastases at the beginning of irradiation. Three of 27 were treated with excisional biopsy, 9 with incisional biopsy or partial resection and in 15 patients biopsies were performed for histology only. The median follow-up of these 27 patients was 17 months (5-66). There was no progression in eight extremity/groin tumors but in 4 of 19 retroperitoneal/pelvic tumors. Three of these were marginal progressions. The actuarial 5-year rate of local tumor control is 64%; the actuarial 5-year survival rate of patients without metastases at the beginning of treatment is 58%. Dynamic spot scan pion irradiation proves to be a successful treatment technique for unresectable sarcomas with a high rate of tumor control and a very low rate of severe late reactions.

Adult↗
PubMed1989

Geographic differences for delay of sexual maturation in Peromyscus leucopus: effects of photoperiod, pinealectomy, and melatonin.

Effects of short-day photoperiod, pinealectomy, and melatonin on sexual maturation were tested in Peromyscus leucopus from either Connecticut (CT) or Georgia (GA). Laboratory reared-stocks from CT and GA were exposed to short daylength (photoperiod) from birth or 25 days of age. At 12 wk of age, delay in sexual maturation was indicated in most CT mice by decreased testis length, combined testes weight, and seminal vesicle weight. Conversely, GA animals did not delay sexual maturation when exposed to short-day photoperiod from either birth or 25 days of age. These results indicate that responses to short daylengths differ for juvenile CT and GA populations. In a second experiment, pinealectomized or sham-operated CT males were exposed to short-day (9L:15D) or long-day (16L:8D) photoperiod from birth. Pinealectomy blocked the effect of short daylength on reproduction. Therefore, the pineal must be involved in the delay of sexual maturation observed for short-day CT mice. The effects of melatonin, a pineal gland hormone, were tested with chronic s.c. implants or daily injections. In CT mice given either melatonin implants or afternoon injections, sexual maturation was delayed. GA mice were insensitive to all melatonin treatments. Further, no differences in circadian organization (phase angle, duration of activity, period under constant dark) between GA and CT animals were apparent. Collectively, these studies indicate that melatonin is involved in the mechanism responsible for delay of sexual maturation in CT mice. Short-day insensitivity of GA Peromyscus leucopus probably results from a deficiency in the melatonin effector pathway and is not due to a disruption of circadian organization.

Animals↗
PubMed1989

Diacylglycerols and PMA induce actin polymerization and distinct shape changes in lymphocytes: relation to fluid pinocytosis and locomotion.

Shape changes have been determined in human blood lymphocytes stimulated with OAG, diC8, PMA, colchicine or the hexapeptide fNLPNTL in short-term assays (30 min). Distinct types of shape-change responses were observed. Colchicine was active in generating a relatively small proportion of polarized lymphocytes (front-tail polarity). OAG, diC8 and PMA produced different types of shape change (non-polar cells with surface projections), and these were closely associated with an increase in actin polymerization and a shift of F-actin into the projections at the cell periphery. The diacylglycerols OAG and diC8 produced biphasic dose-response curves leading to rounding up of cells at very high stimulant concentrations. PMA produced no comparable biphasic response when tested over a much wider concentration range. Though the nonpolar cells with surface projections generated by OAG, diC8 or PMA showed vigorous shape changes, they lacked significant locomotor activity. alpha-Phorbol, 4 alpha-PDD, lumicolchicine or fNLPNTL were inactive. Small blood lymphocytes stimulated by OAG, diC8 or PMA showed a very small increase in the net uptake of FITC-dextran by fluid pinocytosis. Unlike neutrophils, which show a high net uptake, lymphocytes did not concentrate FITC-dextran in large granules, indicating that they do not develop a 'storage' compartment in the form of large vesicles. However, small fluorescent spots were consistently found in at least a fraction of blood lymphocytes. The results indicate that stimulated surface movement may be instrumental in fluid pinocytosis. Diacylglycerols may act as second messengers to induce pinocytosis, shape changes and altered actin polymerization in lymphocytes.

Actins↗
PubMed1989

[How great is the risk of cancer and recurrence following benign breast biopsy?].

Four hundred and thirty-eight patients with biopsy-proven benign breast disease were followed annually in a prospective manner for 4-17 years, to analyze breast cancer risk, correlations with cancer development and recurrence during follow-up. Twelve breast cancers developed in 12 patients during follow-up, giving a 2.6 fold increased cancer risk over the reference population. No association was found between patients who developed cancer and those who did not with respect to the initial histologic feature (p = 0.9), the age at entry by decades (p = 0.4) and relative to menopause (p = 0.3), the presence of cysts (p = 0.5) or calcification (p = 0.2) in the biopsy specimen, a family history of breast cancer (p = 0.7) or the follow-up time (p = 0.9). Benign breast disease does not inevitably lead to recurrence. Moreover, 47% of the 438 patients never had any recurrence and were free of symptoms during follow-up, and 84% never required a further operation. We conclude that an aggressive approach to benign breast disease is not justified, for any type of lesion as defined in this report.

Adenofibroma↗
PubMed1988

[Pion radiation therapy of non-resectable bone- and soft tissue sarcomas at the Swiss Institute for Nuclear Research].

A dynamic, tumor conforming treatment technique ("spot scan") for deep-seated tumors using pions (negative pi-mesons) has been in use at the Swiss Institute for Nuclear Research (SIN) since November 1981. This technique, with a favorable integral dose distribution, allows curative irradiation especially for large, unresectable tumors in the retroperitoneal and pelvic region. Between 1983 and 1986, 26 patients with sarcomas were treated: 18 had soft tissue sarcomas and 8 bone sarcomas. The tumor volumes ranged from 36 to 3400 cc. After previous therapy (23/26 patients) 14 out of 23 patients had progressive disease. In 20 fractions over 5 weeks a total dose of 30-36 Gy (90%-isodose) was administered. In a follow-up period of 9-50 months (median 14 months), the two year local control rate (Kaplan-Meier) for the soft tissue sarcomas was 93.3% and the two year survival rate 67.9%. Each of the 6 patients with bone sarcomas treated with curative intent showed clinically local tumor control. After a total dose of 30-36 Gy, no severe radiation induced morbidity was found.

Adolescent↗
PubMed1988

[Wall calcifications of the left heart atrium].

The chest X-ray of a 61-year-old man with severe aortic and mitral stenosis revealed extensive, circularly arranged calcifications in the wall of the left atrial appendage. He died soon after admission to hospital and autopsy confirmed the atrial calcifications in association with severe mitral stenosis. Although such calcification of the left atrial wall is rare, it can be of importance because it may make the usual surgical approach to mitral valve replacement impossible.

Aortic Valve↗
PubMed1988

Lethal osteogenesis imperfecta: abnormal collagen metabolism and biochemical characteristics of hypophosphatasia.

We have examined collagen from a patient with the rare type IIC form of perinatally lethal osteogenesis imperfecta, in whom biochemical characteristics of hypophosphatasia were also apparent. In addition to normal alpha 1(I) and alpha 2(I) chains, there were chains overmodified along their lengths. Unexpectedly, the thermal stability of molecules containing these chains was normal. This suggests the existence of a structural mutation causing delayed triple helix formation, situated in either the alpha 1(I) or alpha 2(I) C-terminal propeptide. Since collagen synthesised by fibroblasts from each of the patient's parents was normal, the mutation was probably newly arising and dominant. In contrast to other reported cases of lethal osteogenesis imperfecta, not only was the secretion of collagen by cultured fibroblasts considerably retarded, but that of non-collagenous proteins was also severely impaired.

Alkaline Phosphatase↗
PubMed1988

Participation of mitochondrial proliferation in morphological differentiation of murine mastocytoma cells.

Proliferation of a cold-sensitive cell-cycle mutant isolated from an undifferentiated murine mastocytoma line is reversibly arrested at the nonpermissive temperature of 33 degrees C, and the arrested cells undergo morphological differentiation as expressed by the formation of metachromatic granules. Following transfer of these mutant cells from the permissive temperature of 39.5 to 33 degrees C, a transient increase in both cytochrome c oxidase and DNA polymerase gamma was observed, the ratio of total mitochondrial volume to cell volume nearly doubled within 6 days, and numbers of mitochondrial cross-sections per cellular cross-section as determined in electron micrographs underwent a threefold increase. Addition of chloramphenicol (100 micrograms/ml) to the mutant cell cultures 6 days prior to transfer from 39.5 to 33 degrees C prevented the increase in the ratio of total mitochondrial to cell volume. Furthermore, chloramphenicol markedly inhibited the increase in granule number per cell that normally is observed after transfer of cultures to 33 degrees C or during treatment with 1 mM butyrate, suggesting that mitochondrial proliferation may be an obligatory step in the process of morphological differentiation of these mastocytoma cells.

Animals↗
PubMed1988

Long-term follow-up of patients with biopsy-proven benign breast disease.

Three hundred sixty-five patients with biopsy-proven benign breast disease were followed annually in a prospective manner for 4-15 years to analyze breast cancer development, recurrence, and efficacy of management during follow-up. Eleven breast cancers developed in 11 patients during follow-up, giving a 2.6-fold increased cancer risk over the reference population. No association was found between patients who developed cancer and those who did not with respect to the initial histologic feature (p = 0.62), the age at entry by decades (p = 0.40), and relative to menopause (p = 0.54), the presence of cysts (p = 0.87), or calcification (p = 0.74) in the biopsy specimen, a family history of breast cancer (p = 0.80), or the number of observation years (p = 0.27). We conclude that an aggressive approach to benign breast disease is not justified for any type of lesion as defined in this report. Benign breast disease does not inevitably lead to recurrence. Moreover, 41% of our patients never had any recurrence and were free of symptoms during follow-up; 67% never had a mammogram and 82% never required a further operation. There was no association with initial histologic feature in patients who had clinical examination only and those who had mammogram, biopsy, or both during follow-up (p = 0.93). Mammograms were mainly used to clarify a clinical recurrence than as a screening tool, regardless of histologic feature (p = 0.76). Mammograms were mainly used in premenopausal patients (p less than 0.001) having lumps (p less than 0.001), namely, the most difficult patients for radiologic interpretation. This may be one important reason for the rather low sensitivity (75%) and specificity (40%) of mammography in this report. In conclusion, clinical examination is the outstanding investigational tool to follow patients with biopsy-proven benign breast disease, especially in young premenopausal patients.

Age Factors↗
PubMed1988

Granular cystitis in girls. Long-term follow-up.

Granular cystitis or 'papular cystitis' is a very common form of cystitis in young girls. In this paper we show the evolution of this affliction in women after puberty. In a series we were able to follow up leukoplakia or follicular cystitis patients to the age of 16 years.

Adolescent↗
PubMed1988

Determinants of hepatic function in liver cirrhosis in the rat. Multivariate analysis.

We investigated the determinants of hepatic clearance functions in a rat model of liver cirrhosis induced by phenobarbital/CCl4. Aminopyrine N-demethylation (ABT), galactose elimination (GBT), and serum bile acids (SBA) were determined in vivo. The livers were then characterized hemodynamically: intrahepatic shunting (IHS) was determined by microspheres and sinusoidal capillarization by measuring the extravascular albumin space (EVA) by a multiple indicator dilution technique. The intrinsic clearance was determined by assaying the activity of the rate-limiting enzymes in vitro. Hepatocellular volume (HCV) was measured by morphometry. ABT and SBA, but not GBT, differentiated cirrhotic from normal liver. IHS ranged from normal to 10%; all cirrhotic livers showed evidence of sinusoidal capillarization (reduced EVA). The cirrhotic livers showed a bimodal distribution of HCV, HCV being decreased in 50% of the cirrhotic livers. Multivariate analysis showed EVA and portal flow to be the main determinants of microsomal (ABT) and cytosolic (GBT) clearance function; SBA, by contrast, were determined solely by IHS. We conclude that sinusoidal capillarization is the main determinant of hepatic clearance, while serum bile acids reflect intrahepatic shunting. These findings emphasize the importance of alterations of hepatic nutritional flow to explain reduced clearance function in cirrhosis of the liver.

Animals↗
PubMed1988

Diacylglycerol-induced shape changes, movements and altered F-actin distribution in human neutrophils.

The study shows that diacylglycerols (DAGs) as physiological activators of protein kinase C induce characteristic shape changes in human neutrophil granulocytes. In contrast to chemotactic peptides, which can induce front-tail polarity characterized by a contracted tail and an expanding front, DAGs elicit the formation of non-polar cells with surface projections. These cells exhibit a distinct type of motility characterized by vigorous and continuous shape changes without front-tail polarity and without the unidirectional movement and cytoplasmic streaming seen in polarized cells. In neutrophils exposed to DAGs, F-actin is shifted to the cell periphery and mainly into the surface projections of activated cells. DAGs induce the formation of large intracellular vacuoles in neutrophils producing surface projections, and these vacuoles persist after the cells have reacquired a spherical shape. Combined stimulation of human neutrophils with DAG and fNLPNTL results in a suppression of peptide-induced polarity and the formation of non-polar motile cells resembling those stimulated with DAG alone. These results suggest that the diacylglycerol-protein kinase C pathway may be instrumental in transducing or modulating signals to both the locomotor apparatus and the exocytotic and/or pinocytic system of the cell. Neutrophil stimulation with DAGs thus represents a useful model with which to study further the hypothesis that distinct types of neutrophil shapes and movements are preferentially associated with distinct functions and to characterize signalling pathways.

Actins↗