[What influence doe the implant have on the perioperative morbidity following internal fixation of proximal femur fracture? Analysis of dynamic hip screw and proximal femoral nailing]. / Welchen Einfluss hat das Implantat auf die perioperative Morbidität bei osteosynthetischer Versorgung pertrochantärer Femurfrakturen? Analyse von dynamischer Hüftschraube und proximalem Femurnagel.

RATIONALE: Proximal femur fracture is a frequent finding in elderly patients. Both the dynamic hip screw (DHS) and the proximal femur nail (PFN) are established implants. The aim of our study was to assess the perioperative morbidity in a sample of 112 patients with proximal femur fracture, operated on with either DHS or PFN. MATERIAL AND METHODS: Data of 112 consecutive patients (59 DHS, 53 PFN), which consisted of 20 variables, were obtained. Nine variables were selected, which were considered to possess a potential impact on the complication rate. These variables were type of implant, sex, age, period between trauma and surgery, ASA classification, fracture classification of the ASIF, duration of surgery, blood loss, and antibiotics. They were transformed into dichotomous data to enable univariate statistical analysis and logistic regression. RESULTS: The ASA classification only was evaluated to have a predictive value as shown by the odds ratio of 2.23 (90 % confidence interval: 1.09 - 4.56). ASA 3 or 4 patients had an expected frequency, which was 2.2-fold increased as compared to patients classified as ASA 1 or 2, to suffer from perioperative complications. Using logistic regression, again the ASA classification only was shown to have a significant impact (p = 0.066, level of significance: p < 0.1) on the perioperative morbidity. CONCLUSION: As suggested by our results, neither the type of implant nor the other variables mentioned above had a significant impact on the resulting complication rate in our study sample. The ASA classification only was found to significantly increase the probability of an adverse event. This finding should be taken into account prior to initiating therapy.

Role of transforming growth factor alpha and prostaglandins in preferential growth of preneoplastic rat hepatocytes.

The role of transforming growth factor alpha (TGFalpha) and prostaglandins (PGs) in the preferential growth of preneoplastic liver cells was studied. Rats received the genotoxic hepatocarcinogen N-nitrosomorpholine (NNM); placental glutathione S-transferase (GSTp) was used as a marker to identify preneoplastic foci. Preneoplastic foci expressing TGFalpha (TGFalpha(+)) grew more rapidly than TGFalpha negative (TGFalpha(-)) ones. Almost all tumours studied were positive for TGFalpha. The key enzymes of prostaglandin synthesis, cyclooxygenase I (Cox-1) and II (Cox-2), were present in all unaltered and preneoplastic cells and tended to decrease in the later stages of hepatocarcinogenesis. Immunostaining revealed that cultures of hepatocytes, isolated from NNM-treated livers by collagenase perfusion, contained 1-2% GSTp-positive (GSTp(+)) and 9% TGFalpha(+) hepatocytes; 0.6% of the cells were GSTp(+)/TGFalpha(+). Cox-1 and Cox-2 were present in all cells. DNA replication was almost exclusively associated with expression of TGFalpha. GSTp(+) hepatocytes showed a 3- to 4-fold higher probability of TGFalpha expression and of DNA synthesis than GSTp-negative (GSTp(-)) cells. PGE(2) or PGF(2alpha) increased expression of TGFalpha and DNA replication in GSTp(-) cells but not in GSTp(+) cells. PGA(2) and PGJ(2) decreased DNA synthesis in TGFalpha(+) cells without an obvious effect on the intracellular levels of TGFalpha. The Cox-2 inhibitor SC236 suppressed DNA replication preferentially in GSTp(+) cells; this inhibition was reversed by PGE(2)/F(2alpha). Indomethacin had no effect. These results suggest the following conclusions. (i) Growth regulation of preneoplastic GSTp(+) cells in culture exhibits distinct differences from GSTp(-) cells and elevated expression of TGFalpha contributes to their growth advantage. (ii) TGFalpha renders preneoplastic hepatocytes sensitive to suppression of DNA synthesis by PGA(2)/J(2). (iii) SC236, a Cox-2 inhibitor, may have preventive value in hepatocarcinogenesis.

Failure to demonstrate chemoprevention by the monoterpene perillyl alcohol during early rat hepatocarcinogenesis: a cautionary note.

The monoterpene perillyl alcohol (PA) is being considered as a useful chemopreventive and therapeutic agent against human cancers. However, no data are available on the effects of PA in the first stages of hepatocarcinogenesis. To study such effects, putatively initiated cells and preneoplastic foci in hepatocarcinogenesis were used as a model. Male Wistar rats were treated with a single dose of N:-nitrosomorpholine (NNM). Between days 4 and 91 after NNM, subgroups of rats received either PA (1 g/kg body wt/day) or phenobarbital (PB) (50 mg/kg body wt/day) in the diet. Since PA treatment reduced food intake, one control group was fed ad libitum, while a second control was pair fed between days 4 and 91. In order to enhance any treatment effects, all groups, including the controls, were treated with the potent tumor promoter PB after day 91 until the end of the experiment at day 266. Rats were killed at multiple time points and putatively initiated cells and preneoplastic foci were identified by staining positively for placental glutathione S-transferase (G+). The following results were obtained. (i) A few days after NNM treatment single G+ cells emerged; a considerable portion of which developed into foci. (ii) Treatment with PB resulted in an increase in number and size of G+ foci. (iii) PA treatment failed to reduce the number of G+ cells; it somewhat lowered rates of apoptosis in G+ foci and clearly increased their average size. (iv) Eighty-seven days of PA revealed no protective effect on day 266, but, similar to PB treatment, increased the growth of foci. In conclusion, PA exerted no detectable chemopreventive effect in the early stages of rat hepatocarcinogenesis. It rather exerted a PB-like tumor promoting activity. These data argue against a recommendation of PA as a chemopreventive agent for healthy humans.

The influence of amino-reactive substances on contraction threshold of frog skeletal muscle.

The action of the amino-reactive substances pyridoxal phosphate, 4-acetamido-4'-isothiocyanato-stilbene-2,2'-disulfonic acid and 2,4,6-trinitrobenzene sulfonic acid on the contraction threshold, taken as parameter for the initiation of contraction, was investigated in fibers of the sartorius muscle of the frog. The contraction threshold was shifted by 1 to 11 mV to more negative potentials with 1 to 20 mM PDP. Similar shifts from 2 to 17 mV were produced by 0.66 to 20 mM SITS. The threshold shift was only partially reversible. The shift of the contraction threshold obtained with 2 mM SITS was nearly constant at different [Ca2+]o and [Mg2+]o from 1.5 to 50 mM with a tendency to increase at higher divalent cation concentration. TNBS had no effect on the contraction threshold. The action of PDP and SITS on the contraction threshold was successfully described by the surface charge model used earlier to explain the effect of lanthanum, neuraminidase and ruthenium red on the contraction threshold (M. Dörrscheidt-Käfer, Pfluegers Arch. 380:171-179, 181-187, 1979; J. Membrane Biol. 62:95-103, 1981). Here it was assumed that PDP and SITS bind to positive fixed charges on the surface of the T-tubular wall. This results in a shift of the calculated surface potential to more negative values which is thought to account for the measured shift of the contraction threshold.

Comparison of the action of La3+ and Ca2+ on contraction threshold and other membrane parameters of frog skeletal muscle.

The influence of La3+ on contraction threshold, on membrane input resistance, and on action potential parameters was investigated in fibers of the sartorius muscle of the frog, and it was compared to that of Ca2+. The dependence of the contraction threshold on [La3+]0 in the presence of 0.5mM Ca3+ gave a sigmoid relationship between 0.1 and 5 mM La3+ with a shift of 23 to 34 mV to less negative potentials following a 10-fold increase of [La3+]0. The membrane input resistance was increased to various degrees in La-containing solutions, the increase being irreversible. The threshold of action potential generation was shifted to less negative potentials by 28 mV, and the duration at half-maximal amplitude was tripled by 0.5 mM La3+. In comparison a 10-fold increase of [Ca2+]0 in the range of 0.5 to 50 mM shifted the contraction threshold by 15 mV to less negative potentials. 17 mM Ca3+, a concentration having the same effect on contraction threshold as 0.5 mM La3+, increased membrane input resistance reversibly, shifted the action potential threshold by 16 mV to less negative potentials, and had only minor effects on action potential duration. Conduction was never blocked by Ca3+ as it was with 1 mM La3+. In the theoretical treatment, it is shown that the influence of Ca3+ on contraction threshold, but not that of La3+, may be accounted for by its screening and binding to negative surface charges according to the Gouy-Chapman theory of the diffuse double layer. To describe the action of La3+ on the contraction threshold an additional interaction of La3+ with neutral but amphoteric sites was considered.

Excitation-contraction coupling in frog sartorius and the role of the surface charge due to the carboxyl group of sialic acid.

Frog sartorius muscle fibres were incubated with the enzyme neuraminidase which is known to remove surface-bound sialic acids. The sialic acid content of the incubation media was analysed, and the relationship between the threshold of contraction and the altered pH and divalent cation concentration was investigated. The threshold potential of fibres treated with 3.3, 5 or 6.7 units of neuraminidase (at pH 5.5 and 30 degrees C for 2 h) was more positive than that of the control muscle fibres incubated under the same conditions, but without the enzyme. The potential shift is positively correlated with the enzyme concentration and with the amount of sialic acid released. After incubation with 5 units of neuraminidase the potential shift rose to +8.5 mV, depending on [Ca2+]0, [Mg2+]0 and pH. The threshold shift is greatest at low divalent cation concentration (0.5 mM), and not significant at high concentrations of divalent cations (50 mM). In both neuraminidase-treated and control muscles, the effectiveness of Mg2+ is half of that of Ca2+. The dependence of the contraction threshold on pH in the range 5.5--10 is even more pronounced in enzyme-treated than in control muscle fibres. Resting potential, time-course and overshoot of action potential are not affected by treatment with neuraminidase. Threshold shifts are explained by shifts of an external surface potential upon variation of [Ca2+]0, [Mg2+]0 and pH. Treating the muscles with neuraminidase diminishes the net negative charge density, and hence shifts the surface potential to more positive values, by release of negatively charged sialic acid. The different effectiveness of Ca2+ and Mg2+ is ascribed to their different effectiveness of Ca2+ Mg2+ is ascribed to their different binding behaviour towards the negative surface charges.

The interaction of ruthenium red with surface charges controlling excitation-contraction coupling in frog sartorius.

Frog sartorii were incubated in choline Ringer solution containing different amounts of the cationic dye ruthenium red, and were subsequently superfused with ruthenium red-free solution. The contraction threshold was measured during and after the incubation at different calcium and magnesium concentrations. During incubation in ruthenium red the threshold potential is slowly shifted to more positive values depending on time of incubation and the ruthenium red concentration (10--300 microns). After ca. 40 min of incubation a saturation potential is reached. The threshold shift is already maximal (-38mV threshold potential) at 30 microns of ruthenium ret regardless of the calcium concentration up to 5 mM. Omitting calcium from the incubation solution or adding 0.5 mM magnesium instead of calcium resulted in a more negative saturation potential (-48 mV). Washing the muscle in ruthenium red-free solution for 60 min after the incubation fails to reverse the threshold shift completely. The irreversible component of the threshold shift does not depend on the divalent cation concentration during incubation as long as the saturation value during incubation is more positive than -50 mV. The contraction threshold achieved after incubation with ruthenium red is dependent on the divalent cation concentration with calcium being twice as effective as magnesium. The effect of ruthenium red is greatest at small divalent cation concentrations and not significant at 50 mM. Incubating muscles with 5 units of neuraminidase shifted the concentration threshold to more positive potentials to the same extent as incubation with ruthenium red. Subsequent treatment of the neuraminidase-treated muscles with 30 microns of ruthenium red has no further effect on contraction threshold. The alternative experiment, first incubation with ruthenium red and then treatment with neuraminidase, gives the same results. The results are explained by the interaction of ruthenium red with membrane-bound sialic acid. This interaction is thought to result in a decrease in negative charges which results in a shift of the surface potential and hence of the contraction threshold to more positive potentials.

The action of Ca2+ , Mg2+ and H+ on the contraction threshold of frog skeletal muscle: Evidence for surface charges controlling electro-mechanical coupling.

The dependence of the threshold potential for contraction of pH and the concentration of Ca2+ and Mg2+ in the bathing solution was measured in frog skeletal muscle. Decreasing the pH from 10.3 to 4.65 resulted in a threshold shift to more positive potentials. Between pH 6.5 and 8.5 the concentration threshold was almost pH -independent. Increasing [Ca2+]o (in the concentration range 0.5-50 mM) shifted the curves relating contraction threshold to pH to less negative potentials and diminished the overall pH-dependence. The contraction threshold exhibited a similar dependence on [Ca2+]o and [Mg2+]o, the two curves running parallel in the concentration range of 5-50 mM, but Mg2+ was only c. 0.6 as effective as Ca2+. To explain these results a surface charge model is proposed which assumes that two acidic groups, sigma1 and sigma2, and one basic group, sigma3, reside at the outer surface of the membrane of the T-system. Alterations in the extracellular medium exert their influence on the electro-mechanical coupling process by changing the surface potential. The groups will be titrated by protons and their charges screened off by the divalent cations. In addition, Ca2+ was supposed to bind with a weak dissociation constant (23 M) to the two acidic groups. The chosen charge densities are: sigma1 = -0.0085/A2 [= -1e/(10.8 A)2], sigma2 = -0.0037/A2 [= -1e/(16.4 A)2], sigma3 = 0.0028/A2 [= + 1e/(18.9 A)2] with intrinsic dissociation constants KH1 = 10(-2.0)M, KH2 = 10(-4.1)M, and KH3 = 10(-8.5) M. The measured threshold values are satisfactorily described by this model except at extreme alkaline and acid pH values.