Case study: subcutaneous mastectomy. Part I.
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Biomedical subjects
Publications and source records attributed to K Lundberg.
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Using antiserum raised against HMG I, we have shown that HMG I and HMG Y are present in perchloric acid extracts of kidney, lung, heart, brain, liver and intestine in the rat, suggesting that the expression of these proteins may not be dependent upon proliferative activity. The results also show that the ratio between HMG I and HMG Y varies between different organs.
Previous in vitro findings suggest a critical role for the polymorphonuclear leukocyte (PMN) membrane glycoprotein complex CD18 in PMN adherence and chemotaxis. We examined the effect of the murine monoclonal antibody (MoAb) 60.3, recognizing CD18, on induced PMN accumulation in vivo. Rabbits were pretreated with MoAb 60.3, and the chemotactic factors fMLP, leukotriene (LT)B4, and C5a, as well as histamine, were injected intradermally; 4 hours later, plasma leakage (125I-albumin) and the PMN accumulation (myeloperoxidase) were determined. Both PMN accumulation and PMN-dependent plasma leakage were abolished in the inflammatory skin lesions of rabbits pretreated with MoAb 60.3 as compared with control animals, whereas histamine-induced PMN-independent plasma leakage was unaffected. Intravital microscopy of the rabbit tenuissimus muscle revealed that MoAb 60.3 inhibited both PMN adherence in the venules and migration into the tissue following application of LTB4 and zymosan-activated serum (ZAS). Rolling of PMNs along the venular endothelium was unaffected. Thus, these experiments confirm and extend earlier in vitro findings of the critical role of the membrane glycoprotein complex, CD18, in PMN adherence and chemotaxis.
The effects of cerebral ischaemia by carotid artery occlusion and of a ganglionic blocking agent (Arfonad) on cardiac output and regional blood flows were studied after 15 min of haemorrhagic hypotension (mean arterial pressure 50 mmHg) in the rat. The microsphere technique was used for blood flow determinations. Animals subjected to haemorrhagic hypotension and simultaneous carotid artery occlusion (group BC) exhibited a stronger immediate vasoconstrictor response than animals subjected to haemorrhagic hypotension only (group B) and more blood had to be withdrawn to achieve stable hypotension at 50 mmHg (2.6 +/- 0.1 vs. 2.2 +/- 0.4 ml per 100 g body weight (body wt); P less than 0.05). However, group B showed the same decrease in cardiac output as group BC, but the blood flows of the kidneys, spleen, intestine, liver and skin were less deranged at the end of the hypotensive period. Groups B and BC exhibited similar intestinal ischaemic mucosal damage, measured as leakage of [125I]albumin. When induction of haemorrhagic hypotension was combined with ganglionic blockade administration (Arfonad) and carotid artery occlusion (group ABC), significantly less blood had to be withdrawn than in groups BC (1.6 +/- 0.2 vs. 2.6 +/- 0.1 ml per 100 g body wt; P less than 0.05). The blood flows of the kidneys, small intestine, liver, spleen and skin were less compromised in group ABC. In addition, group BC had more profound metabolic acidosis and were more haemoconcentrated than group ABC; moreover, group BC, tended to be hypoglycaemic and showed intestinal mucosal damage, whereas neither of these effects occurred in group ABC.(ABSTRACT TRUNCATED AT 250 WORDS)
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Skin photosensitivity is a side-effect reported for several non-steroidal anti-inflammatory drugs (NSAID). In vitro studies have revealed phototoxic properties in a majority of these compounds with a preponderance for derivatives of propionic acid. Fourteen NSAIDs, the majority commercial preparations in clinical use, have been assayed by the mouse tail technique for in vivo phototoxicity evaluation. Intraperitoneal single doses in the range 12.5-200 mg/kg were given in combination with UVA irradiation for 5 h (total dose 54 J/cm2). The phototoxic reaction was measured 24 h later as the wet weight increase of tail tissue over non-irradiated, drug-treated controls. Four out of 9 propionic acid derivatives were phototoxic: tiaprofenic acid, carprofen, benoxaprofen and naproxen. Among NSAID compounds of other chemical structure only diclofenac and diflunisal were weakly photoactive. The propionic acid derivatives fenoprofen, flurbiprofen, ibuprofen, indoprofen and ketoprofen were negative, as were azapropazone, piroxicam and sulindac among the unrelated compounds. Phototoxicity is one important aspect of NSAID photosensitization. It is advisable to perform predictive studies including in vivo models, such as the mouse tail technique, before new NSAIDs are introduced on the market.
Filter paper blood samples taken routinely from 100 239 newborn infants were radioimmunoassayed five years later for plasma thyrotrophin concentrations. In 32 cases (0.03%) these were found to be raised. Thirty one of these children were traced and subjected to follow up examination by a paediatrician and a psychologist. Of the 31 children, 15 were found to have been receiving treatment for congenital hypothyroidism since a median of 5 months of age (diagnosed group). Of the 16 others, seven children were found to have raised serum thyrotrophin concentrations and were classified as hypothyroid (undiagnosed group). The remaining nine children were euthyroid. Children in the diagnosed group had a mean Griffiths developmental quotient of 87 (control value 103; p less than 0.01), and five out of 13 showed impaired neurological development. Of the remainder, those in the undiagnosed group had a mean developmental quotient of 100 and those in the euthyroid group a mean developmental quotient of 107. In this study achieving a detection rate of congenital hypothyroidism of one in 3000 in a neonatal screening programme resulted in overdiagnosis of about a quarter of patients considered to have true positive findings. This was outweighed, however, by the early identification of all infants with the disease.
A method for concomitant partial hepatectomy and catheterization of the arterial and portal systems of the liver in the rat is described. Catheters were inserted into the gastroduodenal artery and the ileocolic vein. Continuous saline perfusion was performed during 36 hours. In catheterized rats recovery of liver and body weight lagged behind that of non-catheterized rats. The more extensive surgery and the presence of catheters also caused decreased incorporation of 3H-thymidine into liver DNA 24 hours postoperatively. The variation in thymidine incorporation between animals was large. It was shown that by pre-labelling liver DNA with 14C-thymidine the rats can serve as their own controls during acute experiments involving 3H-thymidine, thus reducing the inconsistency of individual variation.
Starch particles injected into the arterial and portal systems of the liver of the rat caused a temporary blockage of the liver circulation and consequent hypoxia in the liver cells. In the regenerating liver this resulted in a 30-40% decrease of thymidine incorporation into DNA, when analysed 1.5 hours after injection. Irradiation-induced cell damage, evaluated by thymidine incorporation 1.5 hours after irradiation with a single dose of X-rays, was not ameliorated by the ischemic condition. It is suggested that this depends on an inhibited nucleotide metabolism and DNA synthesis leading to an additive metabolic hypoxic effect of the starch particles on radiation damage. An equal level of thymidine incorporation, however, was found in an ischemic and a non-ischemic group of animals 16 hours after irradiation. In this case the liver cells in the ischemic group had overcome the additional inhibition of DNA synthesis caused by temporary hypoxia.
Regional differences in dermal inflammatory reactions in the dorsum of rat trunk were studied in three commonly used inflammatory models, i.e., reverse passive Arthus reaction (RPAR), passive cutaneous anaphylaxis (PCA), and histamine-induced inflammatory (HI) reaction. The RPAR showed an increasing severity from cranial to caudal regions, as measured by water content in the skin lesions. The PCA reaction, as measured by Evans blue leakage was not influenced by regional differences. The HI reaction, as measured by water content and leakage of radioactively labeled human serum albumin ( [125I]HSA), was significantly smaller in the central regions of the dorsum than in the most cranial and sacral regions. However, no regional differences were observed when the reaction was evaluated by protein-bound Evans blue leakage. A comparison of the three different methods to determine the HI reaction showed a correlation (r = 0.70) between measurements of water content and [125I]HSA leakage. There was less correlation of these two methods with measurements of Evans blue skin lesion diameter (r = 0.31 and 0.56, respectively). In conclusion, regional differences in inflammatory responses, and methodological differences to measure them, may influence the results of commonly used tests like RPAR, PCA and HI reactions. Such differences should be considered when quantitating dermal inflammatory reactions.
Filter paper blood samples collected neonatally from infants with congenital hypothyroidism were analysed retrospectively for TSH (n = 41) and thyroxine (n = 16). The patients were detected by clinical signs and symptoms and treatment was started during the first two years of life. Similar blood samples from control infants were analysed for comparison. All CH patients would have been detected neonatally if screening had been based on TSH analyses with a cut-off limit corresponding to 50 mU of TSH/l of plasma. A screening programme involving analyses of thyroxine would require considerably higher recall frequency to yield 100% sensitivity. These results support a nationwide CH screening program based on TSH analyses of PKU filter paper blood samples using 50 mU/l of plasma as the cut-off limit.
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This article presents a theory concerning the pathogenetic background for three diseases of civilization: essential hypertension, stable diabetes and atherosclerosis. Man and many other animals have mobilizing mechanisms for preparation for physical activity, expressed inter alia by an increase in blood pressure, hyperglycaemia and hyperlipidaemia. During physical activity, blood pressure falls almost to the resting level and hyperglycaemia and hyperlipidaemia are reduced parallel with the metabolism of glucose and fats in working muscles. In wealthy countries, this preparation for physical activity, which is dominated by the sympathetic-adrenergic system, comes into action just as frequently as in less wealthy countries -- or possibly even more frequently -- but this is rarely followed by muscular activity. How long is this sympathetic dominance maintained? How high are the blood pressure, hyperglycaemia and hyperlipidaemia? How slowly do these return to normal levels? It appears probable that this may be of fundamental pathogenetic significance in the three abovementioned diseases, the causes of which we have difficulty in finding or agreeing upon. Various prophylactic possibilities are mentioned briefly.
BACKGROUND: An analyses of the concentration of arachidonic acid metabolites and the infiltration of leukocytes in the aqueous humour of rabbits after excimer laser keratectomy was performed. The ability of topical diclofenac to block prostaglandin E2 liberation into the aqueous humour was also investigated. METHODS: Photorefractive keratectomy was performed on both eyes of 60 New Zealand rabbits. Prostaglandin E2, 6-keto prostaglandin F1 alpha and thromboxane B2 were detected by radioimmunoassay and leukocytes were counted in the aqueous humour for 120 hours postoperatively. Topical diclofenac was instilled (1 drop/4h) in six animals and prostaglandin E2 was analyzed in the aqueous humour 16 hours postoperatively. RESULTS: The prostaglandin E2 concentration in the aqueous humour increased from 13 in control animals, to 251 pg/100 microliters at 16 hours after treatment (p < 0.05). A statistically significant elevation in the aqueous concentration of 6-keto prostaglandin F1 alpha could not be demonstrated. Thromboxane B2 and leukocytes could not be detected at any time point. Topical diclofenac (1 drop/4h) reduced the levels of prostaglandin E2 in the aqueous humour below 10 pg/100 microliters, 16 hours postoperatively. CONCLUSION: Topical diclofenac (1 drop/4h) inhibited prostaglandin E2 release into the aqueous humour.