Arthroscopic surgery for degenerative knee arthritis and meniscal tears: a clinical practice guideline

The role of arthroscopic surgery in degenerative knee disease was evaluated in this guideline.

Elevated plasma beta-endorphin/beta-lipotropin concentration following a radius fracture.

Plasma beta-endorphin/beta-lipotropin concentration was assessed soon after a fracture. Blood samples from 14 patients with radius fractures were obtained from both arms soon after admission to the hospital (mean 245 min) after the accident. Follow-up samples were taken after healing of the fractures. Higher plasma beta-endorphin/beta-lipotropin concentrations were found in blood samples taken soon after a fracture in both arms compared with the concentrations after healing of the fracture. At admission, mean beta-endorphin/beta-lipotropin concentrations in the fractured and the contralateral arms were 12.7 pmol/L and 13.2 pmol/L, and after recovery 11.1 pmol/L and 11.5 pmol/L (p = 0.012 and p = 0.041), respectively. The pain decreased according to the visual analogue scale (VAS) (0-10) from 4.64 at admission to 0.58 after healing (p < 0.001). In conclusion, this study showed that beta-endorphin/beta-lipotropin concentrations are increased in both arms following a radius fracture compared to the level after the fracture has healed.

Prevalence of Salmonella typhimurium infection in Norwegian hedgehog populations associated with two human disease outbreaks.

Faecal carriage of salmonella was investigated in 320 hedgehogs from Moss municipality in south-eastern Norway, Askøy, Bergen and Os municipalities in central-western Norway, and five municipalities in south-western and central Norway. The sampling in Moss was carried out 1 year after a human outbreak of salmonellosis, whereas the sampling in Askøy, Bergen and Os was carried out during a human outbreak. Both outbreaks were caused by Salmonella Typhimurium 4,5,12:i:1,2. No salmonella were detected in the hedgehogs from south-western (0/115) and central (0/24) Norway. Thirty-nine percent (39/99) of the animals sampled on Jeløy, and 41% (34/82) of those from Askøy, Bergen and Os, carried S. Typhimurium 4,5,12:i:1,2. The PFGE profile of isolates from hedgehogs and human beings were identical within each of the two outbreak areas. A significantly higher carrier rate of S. Typhimurium occurred among hedgehogs sampled at feeding places, compared to those caught elsewhere. The salmonella-infected hedgehog populations most likely constituted the primary source of infection during both of the human disease outbreaks, and the Norwegian hedgehog is suggested as a reservoir host of S. Typhimurium 4,5,12:i:1,2.

Human articular chondrocytes express functional leptin receptors.

The effects of leptin hormone are mediated by interactions with several physiological regulatory systems and the cytokine network, and by targeting cells directly. The leptin receptor is a member of the class I cytokine receptor family, and its signal transduction resembles that induced by many cytokines. We demonstrated that serially cultured human articular chondrocytes possess the leptin receptor (Ob-R), and that this receptor was present on chondrocytes in native human cartilage. In cultured chondrocytes we detected mRNA for the functional isoform of leptin receptor (Ob-Rb or Ob-R(L)), and it was revealed that ligand binding resulted in phosphorylation of signal transducers and activators of transcription, namely STAT1 and STAT5. Chondrocytes stimulated with leptin exhibited an increased proliferation and an enhanced synthesis of extracellular matrix (proteoglycans and collagen). These results indicate that leptin affects cartilage generation directly, which is a novel role for leptin in skeletal growth and development.

[Treatment of focal cartilage injuries in the knee]. / Behandling av fokale leddbruskskader i kne.

Chondrocytes in adult human cartilage have little mitotic capacity even after injuries. Deep injuries penetrating the subchondral bone plate lead to the release of pluripotent mesenchymal stem cells which have the potential to differentiate into different types of connective tissue, including bone and cartilage. The release and stimulation of these stem cells can also be achieved by drilling or microfracture of the subchondral bone of cartilage lesions. When stimulated, periosteal cells may also differentiate into chondrocytes. However, non-chondrocyte determined cells seem to induce mainly fibrocartilage. In 1987 autologous chondrocyte implantation was introduced by a team in Gothenburg. This resulted in clinical improvement and the development of hyaline-like cartilage in patients who had undergone treatment. We first used the method in 1996 in a clinical trial. At a 6-month follow-up of our first 12 patients we found reduced symptoms and improved knee function. This method is promising, but further clinical trials are necessary.

[Accessory soleus muscle as a tumor in the ankle region]. / Aksessorisk soleusmuskel som tumor i ankelregionen.

We report the case of a 21-year ice hockey player with an accessory soleus muscle located medially in the ankle region. The swelling made it increasingly difficult for him to fit his skating boots and caused some pain during play. He was successfully treated by excising the muscle. Previously, the diagnosis was verified surgically in most reported cases. Like most recent authors, we believe that the diagnosis can be confirmed by CT-scan and/or MRI-scan. Surgical excision of the muscle should be reserved for symptomatic cases.

Differential regulation of messenger ribonucleic acids for specific subunits of cyclic adenosine 3',5'-monophosphate (cAMP)-dependent protein kinase by cAMP in rat Sertoli cells.

In the present study we have examined the effects of FSH, forskolin, and (Bu)2cAMP on messenger RNA (mRNA) levels for all known subunits of cAMP-dependent protein kinase in rat Sertoli cells, using newly developed complementary DNA (cDNA) probes. mRNAs for the three regulatory subunits [RI alpha, RII51, (RII beta), and RII54 (RII alpha)] and the catalytic subunit C alpha were shown to be present in cultured rat Sertoli cells, whereas mRNAs for the subunits designated RI beta and C beta were below the level of detection. A high-levelled, concentration-dependent increase in a 3.2 kilobase mRNA for RII51 was observed when cultured immature Sertoli cells were incubated with increasing concentrations of (Bu)2cAMP (10(-6) to 5 X 10(-3) M) for 16 h. Densitometric scanning indicated a maximal stimulation by (Bu)2cAMP of 30- to 40-fold. Incubation with forskolin (100 microM) and FSH (200 ng/ml) gave rise to a smaller but significant increase in mRNA for RII51. When cultured Sertoli cells were incubated in the presence of 10(-4) M (Bu)2cAMP for varying time periods, there was a biphasic regulation of mRNA for RII51. (Bu)2cAMP caused an initial increase in mRNA for RII51 with maximal levels obtained after 10-16 h, after which a time-dependent decrease was observed. For the other three subunits present in Sertoli cells (RI alpha, RII54, and C alpha) a smaller but significant stimulation by (Bu)2cAMP and forskolin (2-4 fold) was seen. The functional implications of these changes in mRNA levels for the different subunits of cAMP-dependent protein kinase have not yet been revealed. However, our data clearly demonstrate differential regulation of the various subunits of cAMP-dependent protein kinase in Sertoli cells. Furthermore, these results document the presence of distinct adaptational changes taking place at the level of cAMP-dependent protein kinase in response to long term elevation of cAMP.

Carcinogenicity of hydroxyalkylnitrosamines in F344 rats: contrasting behavior of beta- and gamma-hydroxylated nitrosamines.

The carcinogenicity of N-nitrosomethyl-(2-hydroxyethyl)amine (NMHEA), N-nitrosomethyl-(3-hydroxypropyl)amine (NMHPA), and the p-toluenesulfonate (tosylate) ester of NMHEA (NMHEATs) was tested in male and female F344 rats. The chemicals (25.6 mumol per application) were administered by twice-weekly gavage in corn oil (0.2 ml) for the lifetime of the animals. NMHEA was found to be an effective carcinogen under those conditions. The median survival time for the females was 9 mo after treatment was initiated, while for the males it was 12 mo. The principal cause of death of the females was hepatocellular carcinoma (14 of 20), while only 6 of 20 male rats exhibited that tumor. A few of the male rats had squamous cell carcinomas of the nasal epithelium (4 of 20), tumors which were not observed in the females. NMHPA was a much weaker carcinogen. Many of these rats survived for 2 yr and most had many age-related cancers. Nevertheless, 10 of the NMHPA-treated males and 2 females had adenocarcinoma of the lung, which was absent in the controls and also induced a significant number of neoplastic nodules in the livers of rats of both sexes. NMHEATs was also a weak carcinogen. However, besides many age-related tumors, it induced some hepatocellular carcinomas as well as hemangiosarcomas of the liver. NMHEATs was at least partially hydrolyzed to NMHEA, which was detected in the blood plasma of treated rats. A hypothesis has been advanced that NMHEA is activated to a proximate carcinogen by sulfate conjugation of the hydroxyl group; the present data do not contradict this hypothesis. The relatively lower carcinogenic potency of NMHPA, the different tumor spectrum induced by this chemical, and particularly the differences in chemical behavior suggest that its mode of activation is not the same as that for NMHEA.

Myeloid hyperplasia in the SENCAR mouse: differentiation from granulocytic leukemia.

The term myeloid hyperplasia has been used interchangeably with many other terms to describe an increased production of granulocytes, megakaryocytes, and erythrocytes in the spleen and other organs in the mouse. This process is occasionally misdiagnosed as granulocytic leukemia. This paper reviews some of the terms used interchangeably with myeloid hyperplasia and describes criteria that can be used to differentiate myeloid hyperplasia from granulocytic leukemia. Additionally, the results of a study in which myeloid hyperplasia was induced following the formation of skin tumors in SENCAR mice is discussed. In this study, positive correlations were found between skin lesions, the spleen weight, and histologic appearance of the spleen. The liver rarely showed microscopic changes of myeloid hyperplasia unless the spleen weighed at least 1.0% of the body weight.

Naturally occurring nonneoplastic histopathological lesions in the female SENCAR mouse.

Lesions that were considered naturally occurring were surveyed in female SENCAR mice used in short-term bioassays. These lesions were encountered in selected target organs and in organs and tissues with gross lesions encountered at necropsy. The genitourinary system was the most frequent site for lesions; cystic ovaries, cystic endometrial hyperplasia, and glomerulonephritis were commonly encountered in this system.

A combined carcinogen bioassay utilizing both the lung adenoma and skin papilloma protocols.

To test the feasibility of employing a combined lung adenoma/skin papilloma assay for broader detection of chemical carcinogenesis than that realized with either bioassay done separately, four strains of mice, SENCAR, BALB/c, A/J, and ICR-Swiss, were administered carcinogens either by the oral or intraperitoneal (IP) routes. The carcinogens administered were ethyl carbamate (EC), benzo(a)pyrene [B(a)P], N-[4-(5-nitro-2-furyl)thiazolyl]formamide (FANFT), and acrylamide (ACR). Starting 2 weeks later, 1 to 5 micrograms (depending on strain) of 12-O-tetradecanoylphorbol-13-acetate (TPA) in 0.2 mL acetone/mouse was applied three times weekly to the shaved back for 20 weeks. All strains displayed increases in the yield of lung adenomas in response to EC at 32 weeks. B(a)P increased lung adenomas in only the SENCAR and A/J strain. Only the SENCAR and ICR-Swiss mice gave positive responses in the skin. In the SENCAR mice, positive response was seen with all four chemicals, however, FANFT gave an inconsistent response. The ICR-Swiss mice responded with an increased skin papilloma yield only to EC. In a separate experiment involving only SENCAR mice, animals were treated with a single oral dose of diethylnitrosamine (DEN) followed by triweekly application of 1.0 microgram TPA. This treatment resulted in 51/57 animals developing lung adenomas vs. 5/57 in the control animals. No treatment-related skin tumors resulted with DEN. Histopathologically confirmed lesions indicate that the spectrum of chemicals detected in the SENCAR mouse may be broadened using a combined bioassay that examines both lung and skin responses.

Gross and microscopic lesions in the female SENCAR mouse skin and lung in tumor initiation and promotion studies.

The skin and lung tissues from SENCAR mice used as part of the Environmental Protection Agency's (EPA's) Carcinogenesis Testing Matrix were examined. This study included SENCAR mice used in three different short-term bioassay protocols in which the skin papilloma assay was used to identify initiators, promoters, and complete carcinogens. Also included were the pathology findings from SENCAR mice used in the combined bioassay in which the skin assay and the lung adenoma assay were conducted simultaneously. The gross and microscopic features of treatment-associated and spontaneous lesions of the skin and lung of the SENCAR mouse used in these studies are defined and the lesions most commonly observed are described. Generally, gross observations and microscopic findings in both the skin and lung tissues were poorly correlated. Although there are several definite criteria on which gross interpretations of the various skin and lung lesions can be made, with the exception of pedunculated squamous cell papillomas and the classic squamous cell carcinomas, the various lesion types had a wide variety of clinical presentations that severely compromised the accuracy of gross diagnosis. Further, in the case of benign skin neoplasms, malignant transformation of these tumors most often occurred at the base of the lesion and was initially hidden from gross observation. As a result, approximately 50% of the neoplasms interpreted clinically as benign tumors (papillomas and keratoacanthomas) were actually malignant neoplasms. Moreover, many lesions determined grossly to be nontumorous were in fact found to be neoplastic when examined microscopically. The SENCAR mouse was found to be more responsive in the lung adenoma assay than other strains examined with exception of the Strain A. Although accurate interpretation of the lung lesions in the SENCAR was compromised by nonneoplastic treatment-associated and/or spontaneous lesions, the feasibility of using the SENCAR skin and lung as target tissues in two-stage combined carcinogenesis studies merits further consideration.

Comparative carcinogenesis by hydroxylated nitrosopropylamines in Syrian hamsters.

The relationship between the chemical structure of nitrosamines and their carcinogenic activity has been examined in Syrian golden hamsters in parallel with similar studies in rats to aid in explaining the sharp interspecies differences in response to these compounds. The relationship between the beta-oxidized N-propyl-nitrosamine structure and the induction of tumors of the pancreatic duct in Syrian golden hamsters was investigated by administration of a number of asymmetric acyclic nitrosamines containing that structure to female hamsters for 29-50 weeks. N-Nitroso-2-oxopropyl-2-hydroxyethylamine (OPE), N-nitroso-2-hydroxypropyl-2-hydroxyethylamine (NIEA), and N-nitroso-2,3-dihydroxypropyl-2-oxopropylamine (DHPOP) induced pancreatic tumors. OPE also induced a high incidence of liver neoplasms, and a number of animals given NIEA and N-nitrosoallyl-2-oxopropylamine (NAOP) also had liver neoplasms. N-Nitroso-2,3-dihydroxypropyl-2-hydroxyethylamine was very weakly carcinogenic. N-Nitroso-2,3-dihydroxypropyl-2-hydroxypropylamine and DHPOP induced a high incidence of neoplasms of the forestomach (mainly papillomas). N-Nitrosoallyl-2,3-dihydroxypropylamine, N-nitrosoallyl-2-hydroxypropylamine, and NAOP induced primarily neoplasms of the nasal mucosa but no neoplasms of the pancreatic ducts in hamsters.

Effect of subsequent treatment of chloroform or phenobarbital on the incidence of liver and lung tumors initiated by ethylnitrosourea in 15 day old mice.

The effect of subsequent administration of chloroform or phenobarbital on the incidence of ethylnitrosourea (ENU) initiated liver and lung tumors was investigated. Fifteen day old Swiss mice were administered ENU, and at weaning they started to receive either 1800 p.p.m. chloroform or 500 p.p.m. sodium phenobarbital in their drinking water. The mice continued to receive either chloroform or phenobarbital until 51 weeks of age. They were sacrificed at 52 weeks of age. ENU at 5 and 20 mg/kg, caused a dose-dependent increase in liver and lung tumors. The male mice were more sensitive to the induction of liver tumors, while no sex preference was observed for the induction of lung tumors. In male mice chloroform inhibited, while in female and male mice phenobarbital promoted spontaneous and ENU-induced liver tumors. Subsequent treatment with either chloroform or phenobarbital did not affect the incidence of ENU-induced lung tumors. In conclusion, when administered in the drinking water, chloroform inhibited while phenobarbital promoted hepatocarcinogenesis in mice.

Carcinogenic effect of nitrosoalkylureas and nitrosoalkylcarbamates in Syrian hamsters.

Three nitrosoalkylureas, two nitrosotrialkylureas, and three nitrosoalkylcarbamates were given to Syrian golden hamsters by gavage at approximately equimolar doses. Measured by the time to death with tumors as an index, nitrosoethylurea was the most potent carcinogen, followed by nitroso-2-hydroxyethylurea, which was less effective in males than in females. The least effective compounds, by this measure, were nitrosooxazolidone and nitroso-5-methyloxazolidone. The remaining compounds, nitroso-N-ethylurethan, nitroso-2-hydroxypropylurea, nitrosomethyldiethylurea, and nitrosotriethylurea appeared to be of similar potency. All of the compounds induced papillomas or carcinomas of the nonglandular stomach in high incidence, except in the groups given nitrosohydroxyethylurea or nitrosooxazolidone; exceptionally, only 35% of the latter group had tumors, compared with 70% or more in the other groups. All of the nitrosoalkylureas induced a high incidence of hemangiosarcomas of the spleen, but the nitrosoalkylcarbamates did not. The quite uniform response of the hamster to these compounds contrasts with the great variety of organs and cell types in which they induce tumors in the rat.

Carcinogenesis by oxygenated nitrosomethylpropylamines in Syrian hamsters.

Three oxygenated propylnitrosomethylamines were administered to female Syrian hamsters at doses similar to those which had induced high incidences of esophageal neoplasms in rats. Nitrosomethyl-2-oxopropylamine (NMOP) given at the rate of 2 mg/animal/week, whether as one application of 2 mg or two applications of 1 mg, led to early death of the animals, mostly with liver neoplasms; administration of 1 mg/animal/week led to longer survival, but most animals died with both liver neoplasms and neoplasms of the nasal mucosa. Only one hamster treated with NMOP had a neoplasm of the pancreatic duct. Of the 14 hamsters treated with the higher dose of nitrosomethyl-2-hydroxypropylamine (NMHP) and surviving beyond 6 weeks, most had liver neoplasms and nine had neoplasms of the pancreatic ducts. At the lower dose of NMHP, most hamsters developed neoplasms of the nasal mucosa, as did those receiving the same dose of NMOP, and seven animals had hemangioendothelial tumors of the liver, but only one animal had a carcinoma of the pancreatic duct. Nitrosomethyldihydroxypropylamine (NMDHP) was a much weaker carcinogen than the other two compounds and induced mainly neoplasms of the nasal mucosa, with little shortening of life.

Carcinogenesis by nitrosomorpholines, nitrosooxazolidines and nitrosoazetidine given by gavage to Syrian golden hamsters.

Five cyclic nitrosamines, four containing oxygen in the ring, were administered by gavage to groups of 20 male Syrian golden hamsters. After administration of very similar doses, nitrosomorpholine, nitroso-2-methylmorpholine and nitroso-5-methyl-1,3-oxazolidine caused the animals to die with tumors after similar times, but nitrosomorpholine induced mainly tumors of the nasal cavity (and a few of the trachea), whereas the 2-methyl derivative induced tumors of the nasal cavity and liver. While nitroso-1,3-oxazolidine and its 5-methyl derivative both induced liver tumors (but no tumors in the nasal cavity) those induced by the former compound took much longer to kill the animals. Nitrosoazetidine, a liver carcinogen in rats, but which had been reported to be inactive in hamsters, did induce tumors of the liver in 30% of hamsters after a much larger dose than the other cyclic nitrosamines.

Comparison of the carcinogenic effectiveness of N-nitrosobis(2-hydroxypropyl)amine, N-nitrosobis(2-oxopropyl)amine, N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine, and N-nitroso-2,6-dimethylmorpholine in Syrian hamsters.

For examination of metabolic interrelationships in carcinogenesis between N-nitroso-2,6-dimethylmorpholine, N-nitrosobis(2-oxopropyl)amine (CAS: 60599-38-4), N-nitrosobis(2-hydroxypropyl)amine (CAS: 53609-64-6), and N-nitroso(2-hydroxypropyl) (2-oxopropyl)amine, each was given to a separate group of 20 female Syrian golden hamsters by gavage. All four compounds induced tumors of the pancreatic duct and lung tumors, but the incidences varied from one compound to another. In addition, N-nitrosobis(2-oxopropyl)amine and N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine induced many hepatocellular and cholangiocellular neoplasms, which the other two compounds did not. On the basis of short time to death with tumors and the relatively low total dose administered, N-nitrosobis(2-oxopropyl) amine appeared to be the most potent carcinogen in the hamster among the four. N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine was next in potency but was considerably weaker than N-nitrosobis(2-oxopropyl)amine. N-Nitroso-2,6-dimethylmorpholine, which was similar in potency to N-nitroso(2-hydroxypropyl) (2-oxopropyl)amine, however, did not induce a significant incidence of liver tumors of any type; and N-nitrosobis(2-hydroxypropyl) amine was considerably less potent than the other three compounds. These results did not support the opinion of N-nitroso(2-hydroxypropyl) (2-oxopropyl)amine as the proximate carcinogenic metabolite of all three compounds in the Syrian hamster but instead suggested that these compounds might have acted through formation of different and yet unknown carcinogenic intermediates.