Accuracy of ultrasonography and magnetic resonance imaging in detecting failure of breast implants filled with silicone gel.

We prospectively studied the accuracy of magnetic resonance imaging (MRI) and ultrasonography (US) for preoperative detection of rupture in 35 single-lumen implants filled with silicone gel in 18 patients. The positive predictive value of US for rupture of an implant was 70% and the negative predictive value 64%. Sensitivity and specificity were 44% and 87%, respectively. Accuracy, defined as the total true positive and true negative values divided by the total number of implants studied was 66%. The positive predictive value of MRI was 100% and the negative predictive value 90%. The corresponding sensitivity and specificity were 88% and 100% and the accuracy 94%. MRI offers significantly better diagnostic sensitivity (p = 0.02) and accuracy (p = 0.004), and should be regarded as the "gold standard" in the evaluation of rupture of breast implants filled with silicone gel. When MRI is not readily available, US is an acceptable alternative.     

The incorporation of different demand concepts in the job demand-control model: effects on health care professionals

This paper reports a study of 212 health care professionals that focuses on job characteristics as predictors of employee health. By means of covariance structure modelling (LISREL 8) we tested the interactive assumptions of the Karasek (1979) Job Demand-Control (JD-C) Model [Karasek, R.A., Jr., 1979. Job demands, job decision latitude, and mental strain: implications for job redesign. Administrative Science Quarterly, 24, 285-307.] using three different concepts of job demands (i.e. psychological job demands, physical demands and emotional demands) in combination with a more focused measure of decision latitude (i.e. job autonomy) to predict employee health (i.e. job satisfaction, job involvement, emotional exhaustion and psychosomatic health complaints). Controlling for gender and age, the results partly support the JD-C hypotheses by finding three out of twelve assumed interaction effects. More specifically, different outcome variables are predicted by different combinations of job autonomy with the three kinds of job demands, respectively. In conclusion, although we refute the central hypotheses of the JD-C model to a large extent, the current (interactive) findings are quite illuminating and will be discussed in the context of their theoretical and practical implications. Researchers as well as practitioners have to broaden their perspective on 'job demands' in health care work and need to focus on different kinds of job demands to capture the complexity of this work setting.     

Effect of glutathione depletion on inhibition of cell cycle progression and induction of apoptosis by melphalan (L-phenylalanine mustard) in human colorectal cancer cells.

Intracellular levels of glutathione have been shown to affect the sensitivity of cells to cell death-inducing stimuli, as well as the mode of cell death. We found in five human colorectal cancer cell lines (HT-29, LS-180, LOVO, SW837, and SW1116) that GSH depletion by L-buthionine-[S,R]-sulfoximine (BSO) below 20% of control values increased L-phenylalanine mustard (L-PAM; Melphalan) cytotoxicity 2- to 3-fold. Effects on kinetics of both cell cycle progression and cell death were further investigated in the HT-29 cell line. BSO treatment alone had no effect on cell cycle kinetics, but did enhance the inhibition of S phase progression as induced by L-PAM; at high concentration of of L-PAM, BSO pretreatment resulted in blockage in all phases of the cell cycle. Yet, BSO pretreatment did not affect the intracellular L-PAM content. L-PAM induced apoptosis in both normal and GSH-depleted cells. A combination of annexin V labeling and propidium iodide staining revealed that even the higher concentration of L-PAM (420 microM) did not induce apoptosis until 48 hr after treatment, but that induction of cell death was markedly accelerated as a result of GSH depletion: 48 hours after L-PAM (420 microM) treatment, GSH-depleted cells showed a 4-fold increase in DNA fragmentation and a 7-fold increase in the fraction of apoptotic (annexin V-positive) cells as compared to cells with normal GSH levels. Various antioxidant treatment modalities could not prevent this potentiating effect of GSH depletion on L-PAM cytotoxicity, suggesting that reactive oxygen species do not play a role. These data show that after BSO treatment the mode of L-PAM-induced cell death does not necessarily switch from apoptosis to necrosis.     

Bremazocine reduces unrestricted free-choice ethanol self-administration in rats without affecting sucrose preference

It has been postulated that opioid systems in the brain may play a role in ethanol reinforcement. In this respect, μ- and δ-opioid receptors may mediate the rewarding effects whereas κ receptors are thought to mediate the aversive effects of opioids. Accordingly, long-acting benzomorphans such as bremazocine, that simultaneously act as μ and δ receptor antagonists and κ receptor agonists may be particularly effective in reducing ethanol self-administration. Therefore, we studied the effect of bremazocine on oral ethanol self-administration in rats using a paradigm [unrestricted free-choice drinking of 10% (v/v) ethanol], previously shown to cause long-term neuroadaptations in the nucleus accumbens and caudate putamen. Bremazocine (0.1 mg/kg, once daily for five consecutive days) reduced ethanol drinking by about 50% during the active period of the animals, whereas the intake of sucrose (3–10% w/v) was affected neither in naive nor in ethanol-experienced rats. This effect of bremazocine appeared not to be secondary to its acute sedative effect or the slight increase in total fluid consumption. Unlike bremazocine, the selective κ-opioid receptor agonist U50,488H (10 mg/kg, once daily) inhibited ethanol drinking only during the first of 5 treatment days and the opioid receptor antagonist naltrexone (0.3–10 mg/kg, once daily) only caused a modest (about 20%) suppression of ethanol drinking during the first hours after drug injection. Thus, bremazocine appears to be far more potent than the clinically applied drug naltrexone in this respect. Our data further support the role of opioid receptors in ethanol reinforcement and indicate that long-acting mixed-action opioids such as bremazocine may be useful as adjuvants for the clinical management of ethanol addiction. Received: 1 July 1998/Final version: 3 September 1998     

Glutathione conjugation of 4-hydroxy-trans-2,3-nonenal in the rat in vivo, the isolated perfused liver and erythrocytes.

The formation of glutathione (GSH) conjugates of racemic 4-hydroxy-trans-2,3-nonenal (4-HNE) in the rat in vivo in the perfused rat liver and rat erythrocytes has been studied. An HPLC system was developed for the assay of 4-HNE-glutathione conjugates (HNE-SG). The very sensitive electrochemical detection method (detection limit 5 pmol) can also be used to study endogenously formed HNE-SG. Three diastereomeric HNE-SG conjugates could be separated by this system. Rat liver cytosol catalyzed the formation of 2 of the 3 conjugates. When 17 micromol/kg [(3)H] 4-HNE was injected intravenously in the rat, 21% of the radioactivity was excreted within 90 min in bile and 37% in urine. Most of the 4-HNE in bile was present as 2 of the HNE-SG conjugates (molecular mass 463). In addition, 25% was excreted as a third GSH conjugate (molecular mass of 461), which was identified as the lactone of the 4-hydroxynonenoic acid glutathione conjugate. Erythrocytes in vitro eliminated 4-HNE very rapidly, in part by GSH conjugation, suggesting that they may also play an important role in vivo. To study the role of the liver selectively, we used the recirculating perfused rat liver without erythrocytes in the perfusion medium; the same conjugates were found, but the third conjugate was a minor component. These results present direct evidence for the in vivo formation of 4-HNE glutathione conjugates in which the liver may play an important role.     

Chemotherapy: principles and application in head and neck tumors

Chemotherapy is a rational treatment modality when microscopic or macroscopic disease is present. Cytotoxic agents can penetrate in all tissues in the body with exception of brain and gonads. They predominantly affect dividing cells. The role of chemotherapy in squamous cell carcinoma in the head and neck area is limited. Indications where chemotherapy can be considered are recurrence after previous surgery and/or radiotherapy and tumours that are not amenable for curative surgery and/or radiotherapy at first presentation.     

Phase II study of intensive chemotherapy with autologous bone marrow transplantation in patients in complete remission of disseminated breast cancer

SummaryBackground This trial studied the disease-free survival after high-dose chemotherapy in patients in complete remission of metastatic breast cancer.Patients and methods Thirty women, mean age 42.2 years (range 33–55) with metastatic breast cancer, received high-dose chemotherapy in a phase II study. Patients were eligible if they were 55 years of age, had achieved complete remission within 6 months of the initiation of chemotherapy, and had a WHO performance scale of 0 or 1. The high-dose regimen consisted of melphalan 180 mg/m² and mitoxantrone 60 mg/m² both divided over 3 days. On day 7 bone marrow and/or peripheral stem cells were infused. After bone marrow recovery, external beam radiation was administered to sites of previous metastatic disease in 15 patients.Results Apart from leuko- and thrombocytopenia, mucositis was the major side effect. One patient died during the bone marrow transplant period due to an aspergillus infection. The median follow-up since highdose chemotherapy is 25 months (range 13 to 56 months). The median disease-free survival since high-dose chemotherapy is 27 months and the disease free survival is still 43% with an overall survival of 53% at 3 years. In two patients tumor relapse occurred only in the brain; in one patient the only relapse sign was a meningeal carcinosis. At the moment 17 patients are disease-free (13+–56+) months after high-dose chemotherapy.Conclusion Until now this high-dose regimen in selected patients with complete remission after induction chemotherapy for metastatic breast cancer has a promising disease free survival.     

The significance of the aminoterminal propeptide of type III procollagen in paroxysmal nocturnal haemoglobinuria and myelofibrosis

The level of the aminoterminal propeptide Col 1–3 of type III procollagen (PC-III) was determined in patients with paroxysmal nocturnal haemoglobinuria (PNH) and primary myelofibrosis (PMF), to study whether PC-III can be used as a parameter for the rate and/or degree of bone marrow replacement with collagen. Normal PC-III levels were found in PNH (6.6±1.1 g/l; N: 8.6±1.8 g/l), while significantly increased levels were found in PMF (24.8±2.2 g/l).During a follow-up of 1 year, a slight increase of 2 g/l occurred in three patients with a stable fibrosis, while one patient with more active disease demonstrated an increase of 25 g/l. Treatment with acetylsalicylic acid led to a decline of PC-III as well as -thromboglobulin level, although normalization did not occur. It was demonstrated by means of gel filtration that the antigens related to the PC-III peptide were heterogenous, and that in PMF at least two main peaks were present, with molecular masses equal to and smaller than PC-III peptide.These data demonstrate that the radioimmunoassay cannot be used for the quantitative determination of PC-III; nevertheless it gives some insight in the process of bone marrow fibrosis.     

Ethnic differences in the anatomical location of colorectal adenomatous polyps

The ratio of right- to left-sided colonic cancer is increasing, but data on the distribution of its usual precursor lesion, the colorectal adenoma, are contradictory. Therefore, we investigated the prevalence of right- and left-sided colorectal adenomatous polyps from January 1, 1970, to September 30, 1989, using the study design of "epidemiologic necropsy" and the autopsy files of The Johns Hopkins Hospital. Compared with the decade of the 1970's, the 1980's showed a slight decrease in the overall prevalence of right-sided adenomas (6.4 per 1,000, 95% confidence limits 4.7-8.8 vs. 5.1 per 1,000, 95% CL 3.6-6.5), but a marked decrease occurred in left-sided adenomas (11.8 per 1,000, 95% CL 9.3-14.3 vs. 6.7 per 1,000, 95% CL 4.8-8.6). As a result, the ratio of right-sided to left-sided adenomas increased from 0.55 in the 1970's to 0.77 in the 1980's. This increased ratio occurred in both sexes, although prevalences were lower in females, and in whites. Unexpectedly, blacks had a ratio of right-sided to left-sided adenomas greater than unity in both the 1970's and 1980's (1.19 vs. 1.79) due to a relatively high prevalence of right-sided adenomas (5.8 per 1,000, 95% CL 3.6-8.0 in 1970's; 5.8 per 1,000, 95% CL 3.3-8.3 in 1980's), but low prevalences of left-sided adenomas (4.9 per 1,000, 95% CL 3.0-6.8 in 1970's; 3.2 per 1,000, 95% CL 1.2-5.2 in 1980's). The overall adenoma prevalence in blacks was lower than in whites. We conclude that the right-sided predominance of colorectal adenomas in blacks suggests ethnic differences in the pathogenesis of colorectal adenomas. This observation may have important implications for secondary prevention of colorectal cancer.     

Fasting increases the susceptibility of rat hepatocytes to the cytotoxic effects of N-hydroxy-acetylaminofluorene. Effects on mitochondrial respiration and membrane potential.

Isolated rat hepatocytes were incubated with the carcinogen N-hydroxy-2-acetylaminofluorene (N-OH-AAF). Cells from fasted rats were much more susceptible to the cytotoxic effects of 1 mM N-OH-AAF than cells from fed rats: after approximately 90 min exposure the former were all dead but the latter still viable. Even after 240 min 25% of the "fed" cells were still viable. The loss of viability was preceded by a decrease in mitochondrial membrane potential (MMP) and inhibition of respiration; the mitochondrial respiration as measured in permeabilized cells appeared uncoupled. Addition of 15 mM fructose prevented cell death and the loss of MMP in cells both from fed and fasted rats to a large extent; however, uncoupling was not prevented. After incubation of hepatocytes from fasted rats with 1 mM [3H]N-OH-AAF for 120 min, 12 nmol [3H]N-OH-AAF became bound per mg cell protein. Addition of fructose decreased this to 7 nmol. In cells from fed animals 4 nmol [3H]N-OH-AAF became bound after 120 min, in this case fructose had no effect. Part of the protective effect of fructose might be explained by a decrease in intracellular ATP, which prevents the formation of reactive intermediates of N-OH-AAF resulting in a decrease of covalent binding, in addition, fructose protects via a yet to be determined mechanism.