Prognostic factors affecting survival in multiple myeloma

70 patients suffering from multiple myeloma were observed by authors in the last 15 years and three months. In the meantime fifty-two out of them have died, and 18 patients are under permanent care. 43 IgG, 17 IgA, 6 Bence-Jones, 2 IgD types were diagnosed according to the paraprotein distribution, one patient proved to be nonsecretory, and an other one to osteosclerotic form as well. The median survival time was 27 months in the group of deceased patients. In the group followed-up 50.8 months survival time was observed up to the closing of the study. Several prognostic factors were investigated. According to the classification by Durie and Salmon the survival time was 60 months in the patients with stage I, 33 months in stage II., and 9 months in stage III respectively. The prognosis is much poorer in patients into the "B" category: the survival time was 14 months. Classified in the basis of the type of the myeloma-cell, the cases with well matured cells have had the best prognosis with survival time of 46 months, while the most unfavourable prognosis was observed in patients with blast-cell type, with a median survival time of 10 months. The greatest number of patients suffered from multiple myeloma of IgG paraprotein type, in this group the serum IgA level was found to be significantly decreased in the patients died due to inevitable infections. The survival was injured significantly by the occurrence of concomitant severe diseases, to.(ABSTRACT TRUNCATED AT 250 WORDS)     

Organ preservation: experience with University of Wisconsin solution and plans for the future

Transplantation of organs continues to be a primary therapeutic modality for treatment of end-stage organ disease, and 1-year graft survival rates show increasing improvements for most organs. A number of transplant centers show 1-yr graft survival rates approaching 90% or more for the kidney, liver and pancreas. Rejection continues to be the major cause for loss of organs and there is still a major shortage of organs for transplantation. Additionally, many organs showed delayed graft function (or primary nonfunction) which may be related to either donor factors or preservation factors. The University of Wisconsin solution for organ preservation has increased the safe time of preservation for the liver, kidney, and pancreas and helped to increase the quality and number of organs available for transplantation. However, the long-range goal of organ preservation (unlimited preservation) is still far from being reached. In the past, preservation could accurately be categorized as an art and preservation solutions were developed based upon theoretical rationales about the mechanisms of organ injury at hypothermia and what agents would suppress injury. The utility and success of this approach is exemplified by the developments of Collins solution and the UW solution. However, further developments in methods to increase the quality and duration of preservation of all transplantable organs would appear to be dependent upon defining, systematically, how organs are injured and what can be done to suppress the injury.(ABSTRACT TRUNCATED AT 250 WORDS)     

Focal hepatic glycogenosis

Foci of altered hepatocytes (FAH) including clear cell foci excessively storing glycogen (focal hepatic glycogenosis) are well known as preneoplastic lesions in animal models of hepatocarcinogenesis induced by chemical, physical or viral agents. The occurrence of similar lesions has been studied in a series of 67 explanted and 2 resected human livers using histological and histochemical approaches. A high incidence of FAH was found in the liver of patients suffering from hepatocellular carcinoma(HCC, 14/14) and liver cirrhosis (21/42). FAH were also detected in one patient each with inborn hepatic glycogenosis type 1a, and cholangiocellular carcinoma. Two patients with focal nodular hyperplasia had FAH-like enzymatic changes within these lesions. No FAH were found in 5 donor livers. FAH excessively storing glycogen including clear and mixed cell foci predominated in most cases with these lesions. The focal hepatic glycogenosis was associated with a significantly increased cell proliferation compared to the extrafocal parenchyma, and with alterations in the activity of various enzymes. In the 175 FAH studied by enzyme histochemistry, two enzymes involved in glycogen breakdown, namely glycogen phosphorylase and glucose-6-phosphatase, showed the most consistent changes, being reduced in 98% and 95%, respectively. In addition, the activities of adenosine triphosphatase and gamma-glutamyltransferase were reduced in 46% and 53% of FAH, respectively. Inconsistent changes were observed in FAH concerning a number of other enzymes. The 14 HCCs investigated histochemically often contained clear cell populations rich in glycogen in well differentiated portions, but were poor in glycogen in moderately and poorly differentiated tumors or tumor components. There were some similarities in the enzyme histochemical pattern of HCC and FAH but also important differences were evident. In contrast to FAH, all HCCs (except one carcinoma of the fibrolamellar type) showed an increase in the activity of the mitochondrial glycerol-3-phosphate dehydrogenase, and 50% of the cases had increased glucose-6-phosphate dehydrogenase activity. The activities of glucose-6-phosphatase and gamma-glutamyltransferase usually showed a reactivation, or even an increase compared to the extrafocal parenchyma, in moderately and poorly differentiated HCCs. Our results indicate that the focal hepatic glycogenosis is a putative preneoplastic lesion in human beings similar to laboratory animals. The focal hepatic glycogenosis appears to be a frequent initial step in neoplastic transformation of hepatocytes, a process associated with a fundamental shift in energy metabolism.     

Some dietary fibers reduce the absorption of carotenoids in women

Dietary fiber may be partly responsible for the lower bioavailability of carotenoids from food than from purified supplements. Due to the lack of detailed information available, we investigated the effects of different kinds of dietary fiber on the absorption of carotenoids and alpha-tocopherol. Six healthy young women received an antioxidant mixture consisting of beta-carotene, lycopene, lutein, canthaxanthin and alpha-tocopherol together with a standard meal. The meal did not contain additional dietary fiber or was enriched with pectin, guar, alginate, cellulose or wheat bran (0. 15 g. kg body weight(-1)). The increases in plasma carotenoid and alpha-tocopherol concentrations were followed over 24 h, and the areas-under-curves (AUC(24h)) were calculated. The mean AUC(24h) of beta-carotene was significantly (P < 0.05) reduced by the water-soluble fibers pectin, guar and alginate with a mean decrease of 33-43%. All tested fibers significantly reduced the AUC(24h) of lycopene and lutein by 40-74% (P < 0.05). The dietary fiber effect on the AUC(24h) of canthaxanthin was almost significant (P = 0.059) and there was no effect on the AUC(24h) of alpha-tocopherol. We conclude that the bioavailability of beta-carotene, lycopene and lutein given within a mixed supplement is markedly reduced by different kinds of dietary fiber.     

Animal models for the optokinetic system of the human]

BACKGROUND: We compare the neuronal and behavioural consequences of abnormal visual experience during early infancy for the optokinetic system of cat and monkey with the neuroopthalmological results in man. MATERIAL AND METHODS: Optokinetic eye movements were recorded with the search coil method and electrooculography. In addition, the response properties of single neurons in the visual cortex and pretectum of anesthetized and paralyzed cats and monkeys were determined in electrophysiological experiments. RESULTS: Our data show that monocular deprivation and strabismus lead to an increase of asymmetry of monocular optokinetic nystagmus and a decrease in gain of slow phase optokinetic eye movements during monocular stimulation as well as to a significant decrease of binocular convergence in the oculomotor system of both cat and monkey. Although these changes are basically similar in both species they are not identical. These differential effects may be explained by structural differences. CONCLUSIONS: Assuming a similar neuronal substrate for the optokinetic system in all primates the monkey represents a more suitable animal model for the human visual system than the cat.     

Evaluation of polyurethane stent implantation for the treatment of complete obstruction of the nasolacrimal system: 8-month follow-up and complications

Dacryocystorhinostomy is still the standard procedure complete stenosis of the nasolacrimal duct. New methods try to preserve the natural lacrimal pathway. Song implanted in 1995 a nasolacrimal polyurethane stent through the nasolacrimal duct. The results and complications of this new method are described in this prospective study. METHODS: Thirty consecutive patients with complete obstruction of the nasolacrimal duct or lacrimal sac were included in the study. The stenosis was localized by dacryocystography. The ages ranged from 22 to 87 years (mean, 58.9 +/- 16 years). Dacryocystography was performed immediately, 4 weeks and 8 months after the procedure to verify the position and patency of the stent. RESULTS: Twenty-five short (35 mm) and 5 long (45 mm) stents were implanted. Twenty-four of 30 patients after 4 weeks and 9 of 10 patients after 8 months had reduced or no complaints. In 1 patient the stent was obstructed. Forceful irrigation with saline solution permitted recanalization. In 1 patient the stent had moved into the upper canaliculus. Because of irritation of the canaliculus it had to be pulled out after 2 months. CONCLUSION: The follow-up is still too short to recommend stent implantation as a real alternative to dacryocystorhinostomy. The main advantages are that the procedure is faster, no incision is necessary, and the local anesthesia is easier. The disadvantage is the need for X-ray examination.     

Strabismus and diplopia as complications after cataract surgery with IOL implantation

Summary In our Department of Orthoptics we have seen an increasing number of patients suffering from diplopia after cataract surgery with IOL implantation. Between 1993 and 1997 the total number of patients with this problem was 24 (2.7 % of all patients, mean age 71 years, age range 38–88). We addressed the question of whether there is a common pattern of motility dysfunction. Methods: After evaluation of the clinical history and the basic ophthalmological findings the following parameters were examined: binocular function (Bagolini test), squint angles (Maddox cross), ocular motility. Results: The 24 patients could be divided up into three groups. Group 1 consisted of 9 patients (mean age 82 years, range 64–88) who complained about diplopia because of strabismus incomitans with vertical deviation and restricted motility on the first day after surgery. In 8 of the 9 patients strabismus surgery was done. Group II consisted of 10 patients (mean age 66 years, range 38–77) who noticed diplopia and strabismus within 7 days after surgery. We found various kinds of heterotropia. Seven of these patients were operated on and two had a prism correction. Group III consisted of 5 patients (mean age 67 years, range 61–78). Their already known strabismus paralyticus or concomitans deteriorated, leading to diplopia in some cases. All patients in this group were operated on. Discussion: For group I we believe that retro-, para- or peribulbar anesthesia caused the motility dysfunction. In groups II and III it is unlikely that local anesthesia had a causative role. The prolonged disruption of binocular vision and the abrupt change in the sensory situation after the cataract operation with lens implantation may be the leading causes for strabismus or deterioration of a preexisting strabism, respectively. Conclusions: These patients need a subtil meticulous diagnostic work-up and follow-up because of the possibility of early surgical therapy, which has a good prognosis. Evaluation of binocular vision and eye movements prior to cataract surgery appears to be helpful for later strabismic surgery.      

The antithrombotic efficacy of the GP IIb/IIIa antagonist SR121787 is potentiated by antithrombin-dependent factor Xa inhibition without an increase in the bleeding risk in the rabbit

Current antithrombotic therapy in acute coronary symptoms is only partially effective and exhibits bleeding complications. These experiments were designed to address the antithrombotic and hemorrhagic interactions of the novel glycoprotein (GP) IIb/IIIa antagonist SR121787 in combination with the indirect inhibitor of factor Xa, SR90107/ORG31540. Thrombogenesis was initiated by electrolytic injury of the intimal surface of the carotid artery, and thrombus formation was assessed by recording carotid blood flow and by measuring thrombus weight 45 min after electrical stimulation. SR121787 was an efficacious antithrombotic agent in this model (ED50 = 16.3+/-0.3 mg/kg, p.o.), whereas heparin (4.5 mg/kg, i.v.) and SR90107/ORG31540 [1 mg/kg (850 aXa anti-units/kg), i.v.] were only marginally effective (17 and 27% inhibition of carotid blood flow reduction, respectively). Coadministrations of heparin (4.5 mg/kg, i.v.) or SR90107/ORG31540 (0.5 mg/kg, i.v.) were found to potentiate the antithrombotic efficacy of threshold doses of SR121787 (5 or 10 mg/kg, p.o.). The enhancement of the antithrombotic efficacy of SR121787 by SR90107/ORG31540 was--contrary to the association of SR121787 with heparin--not accompanied by an increased blood loss from the incised rabbit ear. Coadministrations of heparin or SR90107/ORG31540 did not influence the ex vivo antiaggregatory activity of SR121787. SR121787 coadministration did not alter the systemic anticoagulant activities in heparin or SR90107/ORG31540-treated animals. These data suggest the potential for optimized antithrombotic treatment in acute coronary syndromes when a GP IIb/IIIa antagonist (SR121787) is combined with an antithrombin-dependent factor Xa inhibitor (SR90107/ORG31540).