Post-traumatic stress disorder in international surgeons undertaking trauma electives in a South African trauma centre.

BACKGROUND: Post-traumatic stress disorder (PTSD) is a well-documented psychiatric outcome in patients who experience physical trauma. The phenomenon is less studied in the staff involved in caring for such patients. The aim was to investigate the prevalence of PTSD in visiting international surgeons undergoing elective trauma training and to compare to local and international rates. METHODS: A trauma screening questionnaire (TSQ) survey was conducted among surgeons completing their elective trauma service placements in the Pietermaritzburg Metropolitan Trauma Service. RESULTS: Nineteen surveys were completed (32% response rate). Mean age was 38.9 (SD 6.5). Median postgraduate working experience was 5 (2-10) years. Median time of stay in South Africa was 6 (1-72) months. Compared to preelective experience, there was a five-fold increase in the level of trauma resuscitation experience reported during elective placement. 10.5% of surgeons scored > 5 in the TSQ suggesting probable PTSD. No statistical differences in age, years of prior experience, prior trauma rotation, number of major resuscitations, or length of stay in South Africa were observed in those scoring positive versus negative screening in the TSQ questionnaire. CONCLUSION: Despite being exposed to increased levels of trauma related injury, we observed low rates of positive screening for PTSD in our cohort of visiting international surgeons involved in elective trauma service placements. Investigation of potential protective factors against PTSD in this South African tertiary trauma centre is warranted.

The scourge of knife crime: trends in knife-related assault managed at a major centre in South Africa.

BACKGROUND: Knife wounds are common and represent a major burden to the South African healthcare system. This study reviews trends in spectrum, management and outcome of these injuries at a single trauma centre in KwaZulu-Natal(KZN). METHOD: The regional hybrid electronic registry (HEMR) was reviewed for the period January 2013 - December 2018, and all patients who suffered a knife-related assault were identified and reviewed. RESULTS: During the period under review, a total of 2117 patients suffered a knife-related assault. Regions injured were as follows: head 445, neck 572, face 258, chest 939, abdomen 649, pelvic/urogenital 49, upper limb 418, and lower limb 105. The median ISS was 9 (4-10). Imaging comprised 1242 chest X-rays, 315 abdominal X-rays, 162 abdominal ultrasounds/ FAST, and 929 CT scans of which 634 were CT angiograms. A total of 783 (37%) patients required an operation. The rate of laparotomy was 447/649 (69%) and of thoracotomy/sternotomy/thoracoscopy 95/939 (10%). The rate of vascular exploration for upper and lower limb vascular injury was 101/523 (19%). Mortality was 49/2117 (2.3%).. CONCLUSION: Although our clinical outcomes over this period appear to be consistent, suggesting a familiarity with managing knife-related trauma, the persistently high rate of knife-related injury suggests that we have failed to develop a preventative strategy to try and reduce this scourge.

Trauma electives in South Africa provide valuable training for international surgeons.

BACKGROUND: Trauma electives in South Africa (SA) are common and many foreign-based surgeons have undertaken such electives over the past 3 decades. Despite this, little academic attention has been paid to these electives, which remain largely informal and unstructured. This project aims to redress this deficit. OBJECTIVES: To investigate and document the extent of trauma clinical electives and to assess their impact on the careers of foreign surgeons who have undertaken such electives. METHODS: A mixed methods-style questionnaire was compiled, which sought to document the demographics of surgeons undertaking an SA trauma clinical elective, the trauma clinical experience they had prior to the elective, as well as the volume of experience they acquired during the elective. RESULTS: Sixty questionnaires were sent out and 21 were completed. There were 16 male and 5 female respondents. Only 17 had undertaken a formal trauma rotation before their elective in SA. The mean number of major resuscitations managed prior to rotating through surgery departments in SA was 15, and the mean number managed during a 12-month rotation in SA was 204. It would take each respondent 14 years in their country of origin to acquire an equivalent level of exposure to major resuscitation. During the year before their elective, each surgeon had been exposed to a mean number of the following: 0.5 gunshot wounds (GSWs), 2 stab wounds (SWs), 0.1 blast injuries and 19 road traffic accidents (RTAs). The equivalent mean number for their year in SA was 106 GSWs, 153 SWs, 4 blast injuries and 123 RTAs. The time necessary to achieve a similar level of exposure to their SA experience if they had remained in their country of origin was 213 years for GSWs, 73 years for SWs, 41 years for blast injuries and 7 years for RTAs. Compared with their SA elective, it would take each respondent 3 years to insert as many central venous lines, 9 years to perform the same number of tube thoracostomies, 9 years to manage as many surgical airways, 18 years to explore as many SWs of the neck and 93 years to explore as many GSWs of the neck. Furthermore, it would take 33 years to see and perform as many laparotomies for SWs to the abdomen, 374 years to perform an equivalent number of GSWs to the abdomen and 34 years of experience to perform as many damage-control laparotomies in their countries of origin. In terms of vascular trauma, it would take 23 years to see as many vascular injuries secondary to SWs and 77 years to see an equivalent number of vascular injuries secondary to GSWs. CONCLUSIONS: A trauma clinical elective in SA provides an unparalleled exposure to almost all forms of trauma in conjunction with a well-developed academic support programme. Formalising these trauma electives might allow for the development of exchange programmes for SA trainees who wish to acquire international exposure to advanced general surgical training.

Preparing Japanese surgeons for potential mass casualty situations will require innovative and systematic programs.

INTRODUCTION: The ongoing state of global geo-political instability means that it is prudent to prepare civilian surgeons to manage major military-type trauma. Japan has enjoyed a prolonged period of peace and consequently it is unlikely that surgeons will have been exposed to a sufficient volume of cases. This study reviews the state of trauma training and preparedness in Japan and reviews the trauma workload of a major Japanese emergency medical center and compared with a major South African trauma center with the intention of quantifying and comparing the time needed to gain adequate exposure to major trauma at the two centers. MATERIALS AND METHODS: The literature describing the surgical burden from a number of recent military missions was reviewed and the core surgical skills to manage military-type injuries were identified. We then went on to review all patients admitted to both Kurashiki Central Hospital (KCH) and Pietermaritzburg Metropolitan Trauma Service (PMTS) following trauma between the period September 2015 and August 2016. The burden of trauma at each center was quantified and the number of core surgical competencies or procedures performed at each center was then reviewed. These were then compared with the number of the core procedures which were performed on the reported military missions. RESULTS: Three reports on military surgical missions were reviewed. These came from the Dutch, French and British military surgical services. The average number of each core procedures performed on each reported military surgery mission are tabulated in the text. The most common procedures were wound debridement and orthopedic fixation, followed by trauma laparotomy, neck exploration and thoracotomy. During the 12 month study period, 309 trauma patients were admitted to KCH. Of which 206 (67%) were male, and the mean age was 57 years. There were 10 penetrating injuries and 299 blunt injuries. Of the penetrating injuries there were no gunshot wounds. The mechanisms of injury for blunt trauma were as follows: Road traffic accidents (RTAs); 141 (47%), fall; 136 (46%) and other injuries; 22 (7%). In the same period, 2887 trauma patients were admitted by the PMTS. There were 1244 cases (43%) of penetrating trauma and 1644 cases (57%) of blunt trauma in PMTS. The mechanisms of injury for penetrating trauma were as follows: stab wounds (SWs); 955 (77%), gunshot wounds (GSWs); 252 (20%), and other injuries; 37 (3%) and for blunt trauma were as follows: assault; 739 (45%), RTAs; 669 (41%), fall; 166 (10%), and other injuries; 70 (4%). The exposure to all the key competencies required to manage trauma is overwhelmingly greater in South Africa than in Japan. The length of time needed to obtain an equivalent trauma exposure to that achieved in South Africa, working in Japan is prohibitively long. CONCLUSION: Trauma training in Japan is hamstrung by a lack of clinical material as well as by systematic factors. Training a trauma surgeon is difficult. Developing a trauma system in the country may help address some of these deficits. South Africa in contrast has a huge burden of trauma and sufficient infrastructure to ensure that surgeons working there have adequate exposure to major trauma. Developing an academic exchange program between Japan and South Africa may allow for the transfer of trauma experience and skills between the two countries.

Can We Train Military Surgeons in a Civilian Trauma Center?

INTRODUCTION: The objective of this study was to review the trauma workload and operative exposure in a major South African trauma center and provide a comparison with contemporary experience from major military conflict. MATERIALS AND METHODS: All patients admitted to the PMTS following trauma were identified from the HEMR. Basic demographic data including mechanism of injury and body region injured were reviewed. All operative procedures were categorized. The total operative volume was compared with those available from contemporary literature documenting experience from military conflict in Afghanistan. Operative volume was converted to number of cases per year for comparison. RESULTS: During the 4-year study period, 11,548 patients were admitted to our trauma center. Eighty-four percent were male and the mean age was 29 years. There were 4974 cases of penetrating trauma, of which 3820 (77%) were stab wounds (SWs), 1006 (20%) gunshot wounds (GSWs) and the remaining 148 (3%) were animal injuries. There were 6574 cases of blunt trauma. The mechanism of injuries was as follows: assaults 2956, road traffic accidents 2674, falls 664, hangings 67, animal injuries 42, sports injury 29 and other injuries 142. A total of 4207 operations were performed. The volumes per year were equivalent to those reported from the military surgical literature. CONCLUSION: South Africa has sufficient burden of trauma to train combat surgeons. Each index case as identified from the military surgery literature has a sufficient volume in our center. Based on our work load, a 6-month rotation should be sufficient to provide exposure to almost all the major traumatic conditions likely to be encountered on the modern battlefield.

Insulin and the Brain: A Sweet Relationship With Intensive Care.

BACKGROUND: Insulin receptors (IRs) in the brain have unique molecular features and a characteristic pattern of distribution. Their possible functions extend beyond glucose utilization. In this systematic review, we explore the interactions between insulin and the brain and its implications for anesthesiologists, critical care physicians, and other medical disciplines. METHODS: A literature search of published preclinical and clinical studies between 1978 and 2014 was conducted, yielding 5996 articles. After applying inclusion and exclusion criteria, 92 studies were selected for this systematic review. RESULTS: The IRs have unique molecular features, pattern of distribution, and mechanism of action. It has effects on neuronal function, metabolism, and neurotransmission. The IRs are involved in neuronal apoptosis and neurodegenerative processes. CONCLUSION: In this systematic review, we present a close relationship between insulin and the brain, with discernible effects on memory, learning abilities, and motor functions. The potential therapeutic effects extend from acute brain insults such as traumatic brain injury, brain ischemia, and hemorrhage, to chronic neurodegenerative diseases such as Alzheimer and Parkinson disease. An understanding of the wider effects of insulin conveyed in this review will prompt anaesthesiologists and critical care physicians to consider its therapeutic potential and guide future studies.

Characteristics of Diffusional Kurtosis in Chronic Ischemia of Adult Moyamoya Disease: Comparing Diffusional Kurtosis and Diffusion Tensor Imaging.

BACKGROUND AND PURPOSE: Detecting microstructural changes due to chronic ischemia potentially enables early identification of patients at risk of cognitive impairment. In this study, diffusional kurtosis imaging and diffusion tensor imaging were used to investigate whether the former provides additional information regarding microstructural changes in the gray and white matter of adult patients with Moyamoya disease. MATERIALS AND METHODS: MR imaging (diffusional kurtosis imaging and DTI) was performed in 23 adult patients with Moyamoya disease and 23 age-matched controls. Three parameters were extracted from diffusional kurtosis imaging (mean kurtosis, axial kurtosis, and radial kurtosis), and 4, from DTI (fractional anisotropy, radial diffusivity, mean diffusivity, and axial diffusivity). Voxelwise analysis for these parameters was performed in the normal-appearing brain parenchyma. The association of these parameters with neuropsychological performance was also evaluated. RESULTS: Voxelwise analysis revealed the greatest differences in fractional anisotropy, followed, in order, by radial diffusivity, mean diffusivity, and mean kurtosis. In patients, diffusional kurtosis imaging parameters were decreased in the dorsal deep white matter such as the corona radiata and superior longitudinal fasciculus (P < .01), including areas without DTI abnormality. Superior longitudinal fasciculus fiber-crossing areas showed weak correlations between diffusional kurtosis imaging and DTI parameters compared with tissues with a single-fiber direction (eg, the corpus callosum). Diffusional kurtosis imaging parameters were associated with general intelligence and frontal lobe performance. CONCLUSIONS: Although DTI revealed extensive white matter changes, diffusional kurtosis imaging additionally demonstrated microstructural changes in ischemia-prone deep white matter with abundant fiber crossings. Thus, diffusional kurtosis imaging may be a useful adjunct for detecting subtle chronic ischemic injuries.

Coping strategies and risk of cardiovascular disease incidence and mortality: the Japan Public Health Center-based prospective Study.

AIMS: Coping strategies may be significantly associated with health outcomes. This is the first study to investigate the association between baseline coping strategies and cardiovascular disease (CVD) incidence and mortality in a general population cohort. METHODS AND RESULTS: The Japan Public Health Center-based prospective Study asked questions on coping in its third follow-up survey (2000-04). Analyses on CVD incidence and mortality included 57 017 subjects aged 50-79 without a history of CVD and who provided complete answers on approach- and avoidance-oriented coping behaviours and strategies. Cox regression models, adjusted for confounders, were used to determine hazard ratios (HRs) according to coping style. Mean follow-up time was 7.9 years for incidence and 8.0 years for mortality.The premorbid use of an approach-oriented coping strategy was inversely associated with incidence of stroke (HR = 0.85; 95% CI, 0.73-1.00) and CVD mortality (HR = 0.74; 95% CI, 0.55-0.99). Stroke subtype analyses revealed an inverse association between the approach-oriented coping strategy and incidence of ischaemic stroke (HR = 0.79; 95% CI, 0.64-0.98) and a positive association between the combined coping strategy and incidence of intra-parenchymal haemorrhage (HR = 2.03; 95% CI, 1.01-4.10). Utilizing an avoidance coping strategy was associated with increased mortality from ischaemic heart disease (IHD) only in hypertensive individuals (HR = 3.46; 95% CI, 1.07-11.18). The coping behaviours fantasizing and positive reappraisal were associated with increased risk of CVD incidence (HR = 1.24; 95% CI, 1.03-1.50) and reduced risk of IHD mortality (HR = 0.63; 95% CI, 0.40-0.99), respectively. CONCLUSION: An approach-oriented coping strategy, i.e. proactively dealing with sources of stress, may be associated with significantly reduced stroke incidence and CVD mortality in a Japanese population-based cohort.

Molecular and functional characterization of choline transporter in the human trophoblastic cell line JEG-3 cells.

INTRODUCTION: Choline is essential for the synthesis of the major membrane phospholipid phosphatidylcholine (PC), the methyl donor betaine and the neurotransmitter acetylcholine (ACh), which is involved in several vital biological functions that play key roles in fetal development. In this study, we examined the molecular and functional characteristics of choline uptake in the human trophoblastic cell line JEG-3. METHODS: We examined [(3)H]choline uptake in the human trophoblastic cell line JEG-3. The expression of CTL1 and CTL2 was evaluated by quantitative real-time PCR, western blotting and immunocytochemistry. RESULTS: We demonstrated that JEG-3 cells take up [(3)H] choline by a saturable process that is mediated by a Na(+)-independent and pH-dependent transport system. The cells have two different [(3)H] choline transport systems, high- and low-affinity, with Km values of 28.4 ± 5.0 µM and 210.6 ± 55.1 µM, respectively. Cationic compounds and hemicholinium-3 (HC-3) inhibited choline uptake. Choline transporter-like protein 1 (CTL1) and CTL2 mRNA and protein were highly expressed in JEG-3 cells and were localized to the plasma membrane. DISCUSSION: The present results suggest that choline is mainly transported via a high-affinity choline transport system (CTL1) and a low-affinity choline transport system (CTL2) in human trophoblastic JEG-3 cells. These transporters play an important role in the growth of the fetus.

Impact of reporting rules of biopsy Gleason score for prostate cancer.

AIMS: To investigate how the biopsy Gleason score (GS) and the clinical risk classification have been changed by the reporting rules. METHODS: 565 prostate biopsy specimens were reassessed. Each Gleason pattern, 1 to 5, was interpreted according to the modified Gleason grading system proposed by the International Society of Urological Pathology. The GS for each case was assigned by the previous reporting rules in the institute (OLD rules), applying the overall-scoring, and ignoring a pattern occupying less than 5% and the tertiary pattern. The GS was also assigned according to the NEW rules, applying the highest-core scoring and reflecting a pattern occupying less than 5% and the tertiary pattern. RESULTS: GS upgrading by the NEW rules was observed in 195 (35%) patients. Of these, 179 (92%) patients were upgraded only by applying the highest-core scoring. Of 198 patients with GS 6 by the OLD rules, 22 (11%) were upgraded to GS 3+4. Of 172 patients with GS 3+4 by the OLD rules, 59 (34%) and 28 (16%), respectively, were upgraded to GS 4+3 and > or =8. Of 108 patients with GS 4+3 by the OLD rules, 63 (58%) were upgraded to GS > or =8. As a result, the distribution of D'Amico's clinical risk classification (low, intermediate and high risk) was changed from 26%, 43% and 31% to 23%, 35% and 41%, respectively. CONCLUSIONS: Clinicians should be aware that the reporting rules, especially the highest-core scoring, contribute to a significant upward shift of the biopsy GS and risk classification.

[Pulmonary schwannoma with hypervascularity; report of a case].

A 54-year-old female was admitted to our hospital with a mass shadow in the right pulmonary hilum. The chest computed tomography (CT) scan revealed a well-circumscribed mass in the lower lobe of the right lung. Bronchoscopic examination showed a submucosal tumor in the right basal bronchus which bled easily, and the angiogram showed a tumor with hypervascularity. The tumor was suspected to be a sclerosing hemangioma or malignant tumor. A right basal segmentectomy was performed, and the pathological diagnosis was that of schwannoma. During the 8 year follow-up period, she exhibited no evidence of recurrence.

Effects of carbon dioxide absorbent cooling and temperature gradient reduction on water condensation in the anaesthesia circuit.

BACKGROUND: Large quantities of water condensation occur in the anaesthesia circuit during low-flow anaesthesia. We hypothesized that cooling of the CO2 absorbent would prevent water condensation. METHODS: To cool CO2 absorbent efficiently, we constructed a novel temperature gradient reduction (TGR) canister, which was cooled by a blower. Experiments were divided into three groups: the conventional canister group (control group, n=6), the TGR canister without cooling group (TGR group, n=6), and the TGR canister with cooling group (TGR cooling group, n=6). One kilogramme of CO2 absorbent was placed into the canister. The anaesthetic ventilator was connected to a 3 litre bag and 300 ml min(-1) of CO2 was introduced. About 500 ml min(-1) of oxygen was used as fresh gas. The anaesthetic ventilator was set at a ventilatory frequency of 12 bpm, and tidal volume was adjusted to 700 ml. RESULTS: The longevity of the CO2 absorbent was 437 (sd 7.8) min in the control group, 564 (13.8) min in the TGR group (P<0.001 vs control), and 501 (5.8) min in the TGR cooling group (P<0.001 vs control, TGR). Total water condensation in the anaesthesia circuit was 215 (9.4) mg min(-1) in the control group, 223 (9.7) mg min(-1) in the TGR group, and 47.7 (5.7) mg min(-1) in the TGR cooling group (P<0.001 vs control, TGR). CONCLUSIONS: TGR of CO2 absorbent with cooling is a useful and simple method to reduce water condensation in the anaesthesia circuit in low-flow anaesthesia, with a little increase in the longevity of the CO2 absorbent.

NK105, a paclitaxel-incorporating micellar nanoparticle, is a more potent radiosensitising agent compared to free paclitaxel.

NK105 is a micellar nanoparticle formulation designed to enhance the delivery of paclitaxel (PTX) to solid tumours. It has been reported to exert antitumour activity in vivo and to have reduced neurotoxicity as compared to that of free PTX. The purpose of this study was to investigate the radiosensitising effect of NK105 in comparison with that of PTX. Lewis lung carcinoma (LLC)-bearing mice were administered a single intravenous (i.v.) injection of PTX or NK105; 24 h after the drug administration, a proportion of the mice received radiation to the tumour site or lung fields. Then, the antitumour activity and lung toxicity were evaluated. In one subset of mice, the tumours were excised and specimens were prepared for analysis of the cell cycle distribution by flow cytometry. Combined NK105 treatment with radiation yielded significant superior antitumour activity as compared to combined PTX treatment with radiation (P=0.0277). On the other hand, a histopathological study of lung sections revealed no significant difference in histopathological changes between mice treated with PTX and radiation and those treated with NK105 and radiation. Flow-cytometric analysis showed that NK105-treated LLC tumour cells showed more severe arrest at the G2/M phase as compared to PTX-treated tumour cells. The superior radiosensitising activity of NK105 was thus considered to be attributable to the more severe cell cycle arrest at the G2/M phase induced by NK105 as compared to that induced by free PTX. The present study results suggest that further clinical trials are warranted to determine the efficacy and feasibility of combined NK105 therapy with radiation.

Effects of temperature gradient correction of carbon dioxide absorbent on carbon dioxide absorption.

BACKGROUND: The effects of temperature gradients in CO(2) absorbents on water content and CO(2) absorption are not clear. We constructed a novel temperature gradient correction (TGC) canister, and investigated the effects of temperature gradient correction on the water content and longevity (time to exhaustion) of CO(2) absorbent using a simulated anaesthesia circuit. METHODS: Experiments were divided into two groups according to the type of canister used: the TGC canister (n=6) or the conventional canister (n=6). One kilogram of fresh CO(2) absorbent was placed into the canister. The anaesthetic ventilator was connected to a 3 litre bag and 300 ml min(-1) of CO(2) was introduced. Oxygen (500 ml min(-1)) was used as fresh gas. The anaesthetic ventilator was set at a ventilatory frequency of 12 bpm, and tidal volume was adjusted to 700 ml. RESULTS: Before the experiment, the water content of the fresh CO(2) absorbent in the conventional canister and TGC canister was 16.1 (0.9)% and 15.7 (1.1)%, respectively. After the experiment, the water content of CO(2) absorbent near the upper outer rim of the canister increased to 32.4 (0.7)% in the conventional canister, but increased to only 20.6 (1.3)% in the TGC canister (P<0.01). The longevity of CO(2) absorbent in the conventional canister and TGC canister was 434 (9) min and 563 (13) min (P<0.01). CONCLUSIONS: Temperature gradient correction prevented a local excessive increase in water content and improved the longevity of CO(2) absorbent.

A novel neuroprotective compound FR901459 with dual inhibition of calcineurin and cyclophilins.

Brain ischemia leads to severe damage in the form of delayed neuronal cell death. In our study, we show that the marked neuroprotection of the new immunosuppressant FR901495 in forebrain ischemia is due not only to inhibition of calcineurin, but also to protection against mitochondrial damage caused by mitochondrial permeability transition pore formation through cyclophilin D, one of the prolyl cis/trans isomerase family members. These findings shed light on the clinical application and development of new drugs for the treatment of ischemic damage in the brain as well as in the heart and liver.

Search for novel gene markers of traumatic brain injury by time differential microarray analysis.

Neuronal and glial cell death caused by axonal injury sometimes contributes to whole brain pathology after traumatic brain injury (TBI). We show that neuroprotection by 2 types of immunosuppressants, cyclosporin A (CsA) and tacrolimus (FK506), in a cryogenic brain injury model results from inhibition of calcineurin and protection from mitochondrial damage caused by formation of a mitochondrial permeability transition pore induced by cyclophilin D (CyPD), one of the prolyl cis/trans isomerase family members. We evaluated why CsA is neuroprotective by microarray analysis of gene expression in the cryogenic brain injury rat model. Analyses of expression patterns demonstrated that expression of over 14,000 genes changed between the groups with and without CsA treatment, and about 350 genes among them were extracted showing a significant difference. We learned that the differential expression of several gene targets showed specific patterns in a time-dependent manner. These results may help elucidate the mechanisms of neuronal cell death after TBI and the neuroprotective effects of CsA after TBI.

Cisplatin-incorporating polymeric micelles (NC-6004) can reduce nephrotoxicity and neurotoxicity of cisplatin in rats.

In spite of the clinical usefulness of cisplatin (CDDP), there are many occasions in which it is difficult to continue the administration of CDDP due to its nephrotoxicity and neurotoxicity. We examined the incorporation of CDDP into polymeric micelles to see if this allowed the resolution of these disadvantages. Cisplatin was incorporated into polymeric micelles through the polymer-metal complex formation between polyethylene glycol poly(glutamic acid) block copolymers and CDDP (NC-6004). The pharmacokinetics, pharmacodynamics, and toxicity studies of CDDP and NC-6004 were conducted in rats or mice. The particle size of NC-6004 was approximately 30 nm, with a narrow size distribution. In rats, the area under the curve and total body clearance values for NC-6004 were 65-fold and one-nineteenth the values for CDDP (P<0.001 and 0.01, respectively). In MKN-45-implanted mice, NC-6004 tended to show antitumour activity, which was comparable to or greater than that of CDDP. Histopathological and biochemical studies revealed that NC-6004 significantly inhibited the nephrotoxicity of CDDP. On the other hand, blood biochemistry revealed transient hepatotoxicity on day 7 after the administration of NC-6004. Furthermore, rats given CDDP showed a significant delay (P<0.05) in sensory nerve conduction velocity in their hind paws as compared with rats given NC-6004. Electron microscopy in rats given CDDP indicated the degeneration of the sciatic nerve, but these findings were not seen in rats given NC-6004. These results were presumably attributable to the significantly reduced accumulation of platinum in nerve tissue when NC-6004 was administered (P<0.05). NC-6004 preserved the antitumour activity of CDDP and reduced its nephrotoxicity and neurotoxicity, which would therefore seem to suggest that NC-6004 could allow the long-term administration of CDDP where caution against hepatic dysfunction must be exercised.

[Surgical osteoplasty of the left main coronary artery using the right internal thoracic artery].

A 39-year-old female with a history of progressive refractory angina required medical treatment. A coronary angiography showed 75% left coronary ostial stenosis without any other atherosclerotic lesions. The isolated ostial stenosis of the left main coronary artery was reconstructed by patch angioplasty, using a proximal segment of the right internal thoracic artery. The transaortic patch angioplasty was performed using a superior approach, which allowed a good exposure of the left coronary artery to the aorta without difficulty. A postoperative coronary angiography showed satisfactory patency, and a small biopsy of the ostial tissue demonstrated findings compatible with fibromuscular dysplasia. Based on this outcome, a proximal segment of the internal thoracic artery appears to provide a suitable patch material for enlarging the left coronary ostium.

Little evidence of transdifferentiation of bone marrow-derived cells into pancreatic beta cells.

AIMS/HYPOTHESIS: Bone marrow cells contain at least two distinct types of stem cells which are haematopoietic stem cells and mesenchymal stem cells. Both cells have the ability to differentiate into a variety of cell types derived from all three germ layers. Thus, bone marrow stem cells could possibly be used to generate new pancreatic beta cells for the treatment of diabetes. In this study, we investigated the feasibility of bone marrow-derived cells to differentiate into beta cells in pancreas. METHODS: Using green fluorescent protein transgenic mice as donors, the distribution of haematogenous cells in the pancreas was studied after bone marrow transplantation. RESULTS: In the pancreas of green fluorescent protein chimeric mice, green fluorescent protein-positive cells were found in the islets, but none of these cells expressed insulin. Previous data has suggested that tissue injury can recruit haematopoietic stem cells or their progeny to a non-haematopietic cell fate. Therefore, low-dose streptozotocin (30 or 50 mg/kg on five consecutive days) was injected into the mice 5 weeks after bone marrow transplantation, but no green fluorescent protein-positive cells expressing insulin were seen in the islets or around the ducts of the pancreas. CONCLUSIONS/INTERPRETATION: Our data suggests that bone marrow-derived cells are a distinct cell population from islet cells and that transdifferentiation from bone marrow-derived cells to pancreatic beta cells is rarely observed.