Attitudes of family physicians to alternative medicine]

80 Israeli family physicians (51.25% men and 48.75% women) participated in a telephone survey concerning attitudes, practices and experience with alternative medicine. 23.75% reported practicing 1 or more alternative techniques, most commonly acupuncture (28%) and hypnotherapy (24%). 55% had referred at least 1 patient to an alternative practitioner during the preceding month. Physicians who studied in Israel or Western countries referred more patients than graduates of medical schools of Eastern Europe. Specialists referred patients more often than residents. The most common reason for referral was back pain.     

Therapy of complex I deficiency: peripheral neuropathy during dichloroacetate therapy

A therapeutic trial with polyvitamins and dichloroacetate (DCA) in combination with thiamine in a 13-year-old girl with complex I deficiency is reported. The polyvitamin therapy included thiamine, riboflavin, ascorbate, coenzyme Q 10 and carnitine. This therapeutic regine was used over a period of 17 months without any effect. Although DCA lowered the lactate concentration in blood and CNS--measured by magnetic resonance spectroscopy--no clinical benefit was achieved. After 20 weeks of DCA therapy a distal polyneuropathy with areflexia developed although 100 mg thiamine daily as comedication was given from the beginning of DCA therapy. Nerve conduction velocity of the peroneal nerve was not detectable, sensible evoked potentials of the tibialis posterious nerve were normal. This side-effect resolved completely within 6 months after omission of DCA. Our observation suggests a direct toxic effect of DCA only on the peripheral nervous system in our patient since several cerebral MRI and magnetic resonance spectroscopy studies showed no abnormalities. CONCLUSION. DCA lowers the lactate concentration in children with complex I deficiency of the respiratory chain in a dose of 100 mg/kg body weight without clinical benefit. Reversible peripheral polyneuropathy may develop under DCA therapy despite thiamine medication.     

Port site fascia closure in laparoscopic assisted colectomy: a simple technique

The importance of port site fascia closure after laparoscopic procedures has been recently recognized as an increasing number of port site hernias have been reported. We present a simple technique of port site closure after laparoscopic-assisted colon resections.     

The latest from basic research: mechanisms of metastasis

Mechanisms of transfer of inorganic phosphate, Pi, across the placenta of rats at 21 days of gestation were studied using 32Pi. In one group of experiments the unidirectional transfer of Pi from mother to fetus was estimated from radioactivity in the fetus at various intervals after the tracer injection into the mother. At 15 min after tracer injection, the transfer rate was only slightly higher than the estimated rate of fetal accretion of Pi, and it decreased rapidly with the length of the experiment suggesting deterioration of the transfer mechanism under conditions of an acute experiment. In other experiments, transfer of 32Pi and 51Cr-EDTA (a marker of paracellular transfer) were measured across the dually-perfused placenta in the maternal-fetal direction. The transfer rate of 32Pi was an order of magnitude higher than the transfer of 51Cr-EDTA indicating that most of the Pi transfer is transcellular. The transfer of 32P decreased when the concentration of Na+ in the maternal perfusate was reduced, it was related inversely to the concentration of Pi on the fetal side of the placenta, and it was related directly to the concentration of Ca2+ on the fetal side. The maternal-fetal transfer of Pi exhibited saturation kinetics with a K(m) of about 0.4 mM suggesting that at a physiological concentration of Pi in maternal plasma the transfer mechanism is nearly saturated. The present observations are consistent with Pi being transferred in contransport with Na+. The maternal-fetal transport of Pi appears to be stabilized by the high affinity of the transport system to Pi, and controlled by a negative feedback between fetal concentration of Pi and the Pi transfer rate. It may also be controlled, to some degree, by the fetal plasma Ca2+.     

The critical role of tissue angiotensin-converting enzyme as revealed by gene targeting in mice

Angiotensin-converting enzyme (ACE) generates the vasoconstrictor angiotensin II, which plays a critical role in maintenance of blood pressure in mammals. Although significant ACE activity is found in plasma, the majority of the enzyme is bound to tissues such as the vascular endothelium. We used targeted homologous recombination to create mice expressing a form of ACE that lacks the COOH-terminal half of the molecule. This modified ACE protein is catalytically active but entirely secreted from cells. Mice that express only this modified ACE have significant plasma ACE activity but no tissue-bound enzyme. These animals have low blood pressure, renal vascular thickening, and a urine concentrating defect. The phenotype is very similar to that of completely ACE-deficient mice previously reported, except that the renal pathology is less severe. These studies strongly support the concept that the tissue-bound ACE is essential to the control of blood pressure and the structure and function of the kidney.     

The in vivo effect of hyaluronan associated protein-collagen complex on wound repair

Fetal skin wounds heal without scarring, however the underlying mechanisms remain unknown. Immunohistochemical staining and biochemical studies indicate the deposition of a collagen repair matrix that is highly organized. We have previously described a unique hyaluronan associated protein-collagen complex (HA-PC) profile present during the period of scarless healing in the sheep fetus. In this study, we examined the biologic activity of this HA-PC in an in vivo model of adult rat wound repair. A total of 84 incisional and 84 excisional wounds were examined by histology, TGF-beta immunocytochemistry and computer planimetry (excisional wounds only). Planimetry of the excisional wounds demonstrated the mean wound area remaining at day 1 was 88.7% for the control and 63.6% for the treated (p<0.01). At day 2, mean wound area was 81.5% for the control and 63.6% for the treated (p<0.01). At day 4, mean wound area was 56.6% for the control and 41.9% for the treated (p<0.01). At day 7, mean wound area was 26.9% for the control and 16.8% for the treated (p<0.01). At day 14, mean wound area was 7.9% for the control and 3.4% for the treated (p<0.05). Collagen organization was judged to be greater in the treated compared to control wounds, with a mean organization score of 2.3 vs. 1.9 (p=0.0596; Wilcoxon Signed Rank Sum Test). There were significantly more neutrophils at the wound margin of the treated compared to control wounds, 4.0 vs. 2.7 (p=0.038; Paired Two Tailed Student's t-Test). There was no difference in the number of microphages at the wound margin of the treated compared to control wounds, 6.15 vs. 6.0 (p>0.05). TGFbeta1 and beta2 staining was decreased whereas TGFbeta3 staining was increased in the HA-PC treated wounds. These results suggest that compared to control wounds HA-PC treated wounds heal more quickly, with more organized collagen, more neutrophils at the wound margin and increased TGFbeta3 expression. Furthermore, these data suggest that the manipulation of scarring in adult wounds is possible by the addition of proteins present in fetal skin.     

The dual role of 2-acetylaminofluorene in hepatocarcinogenesis: specific targets for initiation and promotion

The main feature separating a living pacemaker from other oscillators is the fact that the former has not only the oscillatory property but also slow and fast changes of the membrane potential corresponding to the sub- and suprathreshold regions. We propose a simple mathematical model called mRIC and show that the model exhibited the essential feature of pacemakers generating spikes at constant time intervals. The behavior of the model driven by periodic pulse trains is analysed using the phase transition curve.     

TSG-6: an IL-1/TNF-inducible protein with anti-inflammatory activity

The pro-inflammatory cytokines IL-1 and TNF-alpha are primary mediators of the acute phase response, the complex reaction of the mammalian organism to infection and injury. Among the genes activated by TNF-alpha and IL-1 in a variety of cells is TNF-stimulated gene 6 (TSG-6). The TSG-6 cDNA encodes a secreted 35 kDa glycoprotein which is abundant in synovial fluids of patients with various forms of arthritis and detectable in serum of patients with different inflammatory or autoimmune disorders. TSG-6 protein consists of two structural domains: a hyaluronan-binding link module, the characteristic domain of the hyaladherin family of proteins, and a C-terminal CUB domain, present in a variety of diverse proteins. TSG-6 forms a stable complex with components of the plasma protein inter-alpha-inhibitor (I[alpha]I), a Kunitz-type serine protease inhibitor. TSG-6 and I(alpha)I synergize to inhibit plasmin, a serine protease involved in the activation of matrix metalloproteinases which are part of the proteolytic cascade associated with inflammation. Recombinant human TSG-6 protein exerts a potent anti-inflammatory effect in a murine model of acute inflammation. Modulation of the proteolytic network associated with inflammatory processes may be a mechanism whereby TSG-6, in cooperation with I(alpha)I, inhibits inflammation. Activation of the TSG-6 gene by pro-inflammatory cytokines, presence of TSG-6 protein in inflammatory lesions and its anti-inflammatory effect suggest a role for TSG-6 in a negative feed-back control of the inflammatory response.