Monoclonal gammopathy of clinical signifi cance with osteosclerotic lesions - a case report and a literature review.

INTRODUCTION: Multiple myeloma is a common plasma cell neoplasia usually accompanied by the formation of osteolytic foci, whereas osteosclerotic myeloma is a very rare form of plasma cell dyscrasia. When osteosclerotic myeloma is detected, osteosclerotic foci are usually part of the POEMS syndrome. Osteosclerotic myeloma without other manifestations of the POEMS syndrome is an unusual finding. CASE DESCRIPTION: In a 46-year-old woman, osteosclerotic changes of the temporoparietal region caused soft tissue induration over this lesion, which initiated further investigation. Imaging studies subsequently showed multiple osteosclerotic foci in the skull. Examination of blood proteins revealed 8 g/L of IgG-lambda monoclonal immunoglobulin, subclass IgG1. In search of the cause of the osteosclerotic changes, FDG-PET/CT was performed, which revealed no FDG accumulation, i.e., no other tumor (breast or stomach cancer). Low-dose CT showed irregular bone structure, but not significant osteolytic or osteosclerotic foci. To map the extent of osteosclerotic changes, NaF-PET/CT imagination followed, which revealed multiple spots with high fluoride accumulation. A parietal bone biopsy showed osteosclerosis with minor clonal plasma cell infiltration. Trepanobioptic bone marrow sampling revealed an infiltration of bone marrow with atypical plasma cells in 8%. Flow-cytometric examination of bone marrow showed 0,37% of plasma cells, however predominantly (91%) clonal with lambda expression. MRI of the brain identified asymptomatic meningeal thickening. There was no evidence of POEMS syndrome in the patient; thus, we concluded the diagnosis as monoclonal gammopathy of clinical significance with osteosclerosis which was previously termed osteosclerotic multiple myeloma. CONCLUSION: Monoclonal gammopathy of clinical significance (MGCS) with osteosclerotic skeletal changes, documented on CT and multiple foci with intensive osteoneogenesis, documented on NaF-PET/CT without evidence of POEMS syndrome, is an extremely rare form of plasma cell dyscrasia. This publication documents the unique clinical manifestations of IgG-lambda type plasma cell proliferation without signs of POEMS syndrome and the role of NaF-PET/CT imaging. Classification of this disease as MGSC with osteosclerotic manifestations is more consistent with the indolent nature of the disease with a significantly better prognosis, compared with multiple myeloma.

Dynamic MR based analysis of tumor movement in upper and mid lobe localized lung cancer.

BACKGROUND AND PURPOSE: Tumor motion is a very important factor in the radiotherapy of lung cancer. Uncertainty resulting from tumor movement must be considered in 3D therapy planning especially in case of IMRT or stereotactic therapy. The aim of our dynamic MR based study was to detect tumor movements in upper and mid lobe lung tumors. PATIENT AND METHODS: Twenty-four patients with newly diagnosed stage II-IV lung cancer were enrolled into the study. According to tumor localization in the right S1-S3 segments 9, in the right S4-S6 segments 2, in the left S1-S3 segments 9 and in the left S4-S6 segments 4 lesions were detected. In normal treatment position individual dynamic MR examinations were performed in axial, sagittal and coronal planes (100 slices/30 sec). For tumor motion analysis E-RAD PAC's software was used. RESULTS: Movements of the tumor under normal breathing conditions were registered in the three main directions. The mean antero-posterior deviation was 0,109 cm (range: 0,063 cm-0,204 cm), the mean medio-lateral deviation was 0,114 cm (range: 0,06 cm- 0,244 cm). The greatest deviation was measured in cranio-caudal direction (mean: 0,27 cm, range: 0,079 cm- 0,815 cm). The mean direction independent deviation was 0,18 cm (range: 0,09 cm- 0,48 cm). CONCLUSION: Dynamic MR is a sensitive and well tolerated method for tumor motion monitoring in high precision 3D therapy planning of lung cancer patients. Our results demonstrate that tumors located in the upper and mid lobes have moderate breath synchronous movements. The greatest deviation occur in cranio-caudal direction.

[Comparison of human milk with 3 different types of infant food in the nutrition of full-term neonates]. / Az anyatej és három különbözö tápszer összehasonlító vizsgálata érett újszülöttek táplálásában.

Healthy, term infants who were either breast-fed, or received conventional formula (Mildibé, EGIS; Pre-Aptamil, Milupa), or a formula containing hydrolyzed proteins (Aptamil H. A., Milupa) were investigated. Each group consisted of 10 infants who were fed ad libitum. Somatic development (gain in weight, length and head- and chest circumferences), serum Ca and P levels, alkaline phosphatase activities and basic biochemical parameters of protein metabolism (serum total protein, albumin, uric acid, creatinine and urea nitrogen levels) were determined at the ages of 2, 4 and 8 weeks. Anthropometric measurements did not reveal considerable differences between the groups investigated. At the age of four weeks, serum calcium levels were significantly higher in the breast-fed infants than in those receiving formula. Both at the ages of four and eight weeks, serum total protein levels were significantly lower in the infants receiving the formula consisting of hydrolyzed proteins than in the breast-fed controls. No difference of considerable extent was seen in the other biochemical parameters measured. The results obtained indicate that, in the lack of the possibility of breast-feeding, all the three formulae investigated can be used as substitute of breast milk.

The antineoplastic drugs dose dependently inhibit the healing of subacute gastric ulcer produced by punching in rats.

The aim of present study was to investigate the effects of some antineoplastic drugs on the healing process of subacute gastric ulcer, produced by punching, in rats. We determined the doses which inhibit the healing rate by 50%. Our results confirm the general observation that present applied anticancer drugs cannot distinguish between normal and tumor cell proliferation. The ID50 values of tested drugs strongly correlate with human doses.

The influence of metoclopramide on the composition of human breast milk.

UNLABELLED: The breast milk prolactin (PRL) has been claimed to play a role in the control of electrolyte composition of the milk. Since metoclopramide has been shown to increase milk production in humans, we have made an attempt to investigate the production, the PRL and sodium concentrations in milk with (group I) and without (group II) maternal metoclopramide treatment (5 days, 30 mg/day). Both groups consisted of 11 mothers and their full-term newborn infants. The daily milk production was significantly higher in the treated group (276.4 +/- 36.6 vs 150.9 +/- 25.3 ml/day, p less than 0.01). The PRL measured by RIA was similar in the milk samples of the metoclopramide treated and control groups (80.5 +/- 17.7 vs 90.7 +/- 27.3 ng/ml). The sodium concentration in the milk of mothers taking metoclopramide was 22.1 +/- 1.6 mmol/l and 24.3 +/- 3.2 mmol/l in the control group (p = 0.59). On the 5th postnatal day the plasma PRL of the newborns of mothers treated with metoclopramide does not differ from the values of the control babies (29.8 +/- 2.6 vs 30.7 +/- 2.4 ng/ml) indicating that the amount of metoclopramide transferred into the milk has no apparent influence on the hypothalamo-hypophyseal axis of the neonate. IN CONCLUSION: the maternal metoclopramide treatment augments the milk production without having any effect on the PRL and sodium concentration of human "mature" milk.

GABAA receptors in the rat stomach may mediate mucoprotective effects.

The occurrence and characteristics of binding sites specific for gamma-aminobutyric acid (GABA) and muscimol in the rat stomach were examined by biochemical and autoradiographic techniques, and the effects of GABAergic model compounds on gastric ulceration induced by chemical irritation was studied in intact and unilaterally vagotomized rats. Specific binding sites for [3H]GABA and [3H]muscimol, which showed the characteristics of GABAA receptors, were demonstrated on gastric membranes. Specific muscimol binding sites were found in all regions of the stomach and were present in both the mucosal layer and the remaining tissue of the stomach. Oral pretreatment of the rats with GABA, selective GABAA receptor agonists, or inhibitors of GABA degradation protected the gastric mucosa against the ulcers induced by acidified ethanol (chemical irritant), in both intact and vagotomized rats. These findings are consistent with the view that a subpopulation of GABAA receptors in the rat stomach may mediate the anti-ulcer effect.

Effect of cytoprotective and antiulcer drugs on the healing process of subacute gastric ulcer in rat (a new model).

It has been developed by us a simple new method for producing subacute gastric ulcer in rats, combined with a novel method for the quantitative evaluation of the healing process. Fasted rats with 120-150 g were used. The animals were anaesthesized by ether and than a polyethylene chateter was orally inserted into the stomach with a fine needle inside. After the cannule reached the gastric wall, the needle was pressed gently so as to punch the gastric wall. Drugs under study were administered orally 30 min and 24 h after the puncture. Food and water were given ad libitum from 2 h after the intervention until the end (96 h) of experiments. In order to follow the healing process of subacute ulcer, the so-called tensile strength of the ulcer was determined by inflating and expressed in mmHg. The healing rate was calculated. The antiulcer drugs: Cimetidine, Famotidin, Pirenzepine and sucralfate dose dependently and significantly increased the healing rate of ulcer. Non steroidal antiinflammatory drugs: naproxen, piroxicam, indomethacin and ibuprofen significantly delayed the healing of ulcer. ASA showed tendency to delay the healing. Strong HCl (0.5 molar) significantly delayed the healing of ulcer. N-EM given subcutaneously dose dependently delayed the healing of subacute ulcer.

Novel method for producing standard subacute gastric ulcer in rats and for the quantitative evaluation of the healing process. Effect of several drugs on healing.

A simple new method has been developed for producing subacute gastric ulcers in rats, and it has been combined with a novel method for the quantitative evaluation of the healing process. Fasted rats of body weight 120-150 g were used. The animals were anaesthesized by ether and then a polyethylene catheter was orally inserted in the stomach with a fine needle inside. After the cannula reached the gastric wall, the needle was pressed gently so as to punch the tastric wall. Drugs under study were administered orally 30 min and 24 hr after the puncture. Food and water were given ad libitum from 2 hr after the intervention until the end (96 hr) of experiments. In order to follow the healing process of subacute ulcer, the so-called tensile strength of the ulcer was determined by inflating and was expressed in mmHg. The healing rate was calculated. The antiulcer drugs, cimetidine, famotidin, pirenzepine, and sucralfate, dose dependently and significantly increased the healing rate of ulcer. Nonsteroidal antiinflammatory drugs, naproxen, piroxicam, indomethacin, and ibuprofen, significantly delayed the healing of ulcer and acetylsalicylic acid showed no significant effect on the healing. Strong HCl (0.5 molar) significantly delayed the healing of ulcer. N-EM given subcutaneously dose dependently delayed the healing of subacute ulcer.

Cysteamine protects against diarrhoea induced by castor oil. This protective effect can be potentiated by SH-alkylator treatment.

Cysteamine given orally or subcutaneously protects against diarrhoea induced by castor oil. Pretreatment with N-EM, an SH-alkylator, does not influence the occurrence of diarrhoea. Furthermore, N-EM pretreatment does not influence the protective effect of loperamide or difenoxilate. However, N-EM pretreatment potentiates the protective effects of cysteamine or indomethacin against diarrhoea. These findings indicate that sulfhydryl-sensitive processes may also be involved in the mechanisms of diarrhoea.

Quantitative analysis of intestinal ulceration induced by indomethacin, in rats.

It has been developed a new simple method for the evaluation of intestinal ulceration induced by indomethacin or other drug in rats. It is well known that the erosion caused by ulcerogenesis leads to the weakening of the strength of the intestinal wall. Simply measuring the tensile strength of intestinal wall, by inflatation, in the experimental animals provides quantitative indices of the severity of ulceration.

Sodium-salicylate in contrast with acetylsalicylic acid prevents gastric antral and intestinal ulcers produced by indomethacin in the refed rat.

Indomethacin produced true ulcers; the lesions penetrated into the muscularis mucosae of the antrum of refed rats and into the intestine of both refed and conventionally fed rats. Sodium-salicylate dose-dependently and simultaneously prevented the antral and intestinal ulcers produced by indomethacin in refed rats. Acetylsalicylic acid had no preventive effect on small intestinal ulcers and markedly increased the indomethacin induced antral ulcers.

Gastrointestinal cytoprotection by indomethacin + sodium salicylate combination in rat.

Non-steroidal antiinflammatory agents are well known to cause gastrointestinal damage in many species including the rat and human. Pelsonin a combination of indomethacin and sodium salicylate (1:10 ratio) has a cytoprotective effect against acidic-alcohol induced gastric necrosis, and it does not induce intestinal ulceration. Pelsonin is capable of blocking the formation of intestinal ulcers induced by oral indomethacin 10 mg/kg (curative cytoprotection). The cytoprotective potency of Pelsonin is due to sodium salicylate.

Comparative pharmacology of a 1:10 combination of indomethacin-sodium salicylate.

It has been found that gastrointestinal side-effects of indomethacin could be abolished when administered in combination indomethacin:sodium salicylate (ratio 1:10). In this paper comparative pharmacological data of this combination and its basal compounds are presented. Acute toxicity of the combined preparation was 72 times less in rats than that of indomethacin alone. All therapeutic indexes were markedly increased in the combination of indomethacin-sodium salicylate compared with the separate drug treatments.

Tape test as a simple new method for the study of compounds increasing the problem-solving ability of the rat.

A simple new method, the "tape test" has been developed for studying the enhancement of learning by drugs in "learning-dull" rats. A piece of adhesive tape is pressed on the left front pad of the rats. The time of tape removal by the animal, i.e., the problem-solving time is measured. In our experiments the selected learning-dull rats were used which were unable to remove the tape within 60 s observed on 3 consecutive days. The problem-solving ability of the rats was studied on 4 consecutive days, by posttrial administration. The problem-solving ability was found to be increased after treatment with different drugs such as para-chlorphenylalanine (PCPA), pemolin, orotic acid, vitamin B12. The stimulatory effect of vitamin B12 could be inhibited by vincristine.