A cerebrospinal fluid (CSF) pseudocyst can rarely occur in the breast. It usually results from damage to a ventriculoperitoneal (VP) shunt during a mammogram or augmentation breast surgery. If fluid collection is seen in close proximity to the VP shunt, it should raise the suspicion of a CSF pseudocyst. Cystic lesions in the breast are classified as simple, complicated, and complex. A cerebrospinal fluid (CSF) collection is an uncommon cause for a simple/complicated cyst in the breast. We report one such unusual case with classic imaging features on USG.A 24-year-old female presented with a swelling in the right breast of 4 days' duration. There was no history of fever. USG showed a cystic lesion at the 9 o'clock position . The cyst wall was very thin and debris was seen in the dependant part of the cyst . A tube-VP shunts are placed to decompress an obstructed CSF drainage pathway. CSF is tShunt dysfunction could be due to disconnection, infection, obstruction, or migration of the tube. A pseudocyst results due to leak from the drain tube, which can occur anywhere in its course. Most pseudocysts 3.2%) are seen in the abdomen.2 A CSF p% are seeThe common differential diagnosis of a cystic lesion in the breast includes simple cyst, abscess, oil cyst, galactocele, fibroadenoma, intracystic papilloma, atypical ductal hyperplasia, infiltrating ductal carcinoma, and infiltrating lobular carcinoma. Cysts in43A CSF pseudocyst is a rare cause of breast mass. It should be considered in any patient with a history of VP shunt. USG is the modality of choice in such cases. Special care should be taken while performing mammography in a patient with a history of VP shunt because the procedure can cause tube rupture and lead to the formation of a CSF pseudocyst.


Retinol-binding protein 4 (RBP4) is a recently identified adipokine that is elevated in the serum in several insulin-resistant states. We investigated the relationship between non-alcoholic fatty liver disease (NAFLD) and serum RBP4 in nondiabetic adults.n = 73; 45 males and 28 females) or a normal group  was based on the presence of fatty liver disease determined by sonography.One hundred and fifty-nine nondiabetic, non-alcoholic subjects  participated in this study. Division of subjects into a NAFLD group . Multiple logistic regression analysis revealed that the RBP4 level was an independent factor associated with NAFLD (P = 0·0042). In addition, serum RBP4 levels were positively correlated with serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ-glutamyltranspeptidase (GGT) levels. The significant association between serum RBP4 and GGT levels remained even after adjusting for age, gender, body mass index, the homeostasis model of assessment (HOMA) value and the presence of NAFLD .Serum RBP4 levels in the NAFLD group were significantly higher than those in the normal group (62·8 ± 16·0 mg/l Serum RBP4 levels are significantly associated with NAFLD and liver enzymes. Non-alcoholic fatty liver disease (NAFLD) is a major liver disease found throughout the world. It has a broad spectrum of manifestations ranging from simple steatosis to non-alcoholic steatohepatitis and cirrhosis.8et al. have reported that elevation of serum RBP4 causes systemic insulin resistance, and reduction of serum RBP4 improves insulin action in mice.Retinol-binding protein 4 (RBP4) is a newly identified adipokine that is elevated in the serum in several insulin-resistant states.n = 14) using Western blot analysis of RBP4. The RBP4 concentrations by Western blotting correlated with the results of the AdipoGen ELISA kits .The participants in this study were recruited from individuals who were self-referred for a routine health check-up at Korea University Ansan Hospital. The medical health check-up provided by the hospital included an abdominal ultrasound. We enrolled patients found to have a fatty liver. Thereafter, we selected subjects who did not have a fatty liver, matched for age and gender, as controls. Subjects were excluded from this study if they met any of the following criteria: (i) alcohol drinking >140 g/week; (ii) a positive test for hepatitis B surface antigen or hepatitis C antibody; (iii) evidence of toxic hepatitis; (iv) presence of previously diagnosed diabetes or fasting glucose ≥ 7·0 mmol/l; (v) other endocrine disease (e.g. thyroid dysfunction); (vi) known liver or renal dysfunction; or (vii) age < 20 or > 80 years. All subjects denied taking drugs known to promote fatty liver disease or to cause insulin resistance over the past 3 months. As a result of the baseline investigations including the abdominal ultrasound, 73 subjects  with fatty liver and 86 healthy subjects  matched for age and gender as normal controls were enrolled in this study. Informed consent was obtained from all subjects before enrolment in the study, which was approved by the ethics committee of the institution. Clinical data such as age, gender, height, weight and body mass index were recorded. Systolic and diastolic pressures were measured by a baumanometer  on the arm of a seated subject who had rested in a sitting position for 10 min before the measurement. Body fat mass and body fat percentage were measured by bioelectrical impedance analysis . Waist-to-hip ratio (cm/cm) was determined by measurement of the circumference of waist and hip in the standing position. Waist circumference was measured to the nearest 0·1 cm at the level of the iliac crest by a tape while the subject was at minimal respiration. Hip circumference was measured at the level of the anterior superior iliac spine. Blood samples were drawn after an overnight fast and immediately centrifuged. Serum total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, uric acid and liver enzyme levels were determined by enzymatic methods with a chemistry analyser . Plasma glucose was measured by the glucose oxidase method. High-sensitivity C-reactive protein (hsCRP) was determined by nephelometry . Serum insulin was measured with an insulin radioimmunoassay kit , which had a reactivity of less than 0·2% to human proinsulin. Insulin resistance was estimated using the homeostasis model of assessment (HOMA), calculated as fasting glucose (mmol/l) × fasting insulin (mU/l)/22·5.A fatty liver was diagnosed on ultrasonography by a single experienced radiologist who was blinded to the laboratory data. Of the four known criteria used for the diagnosis of fatty liver , the participants were required to have hepatorenal echo contrast and liver brightness for the diagnosis of fatty liver.n (%). Variables that were skewed to the right were log-transformed for subsequent analysis. Differences between mean values of the NAFLD and normal groups were examined using the Student's t-test or χ2 test. The association of RBP4 with NAFLD was investigated using the multiple logistic regression analysis that was adjusted for age, gender, body mass index, waist circumference, body fat per cent, systolic and diastolic pressure, fasting glucose, HOMA, total cholesterol, triglycerides and HDL cholesterol. Pearson's correlation analysis was performed to establish the relationship between RBP4 and anthropometric, metabolic parameters and various liver enzymes in all subjects and then evaluated by gender. Statistical significance was accepted for P-values of < 0·05. All statistical analyses were performed using sas version 9·13 .Data for anthropometric and metabolic characteristics of the study subjects were expressed as means ± SD or P < 0·0001). Male participants had higher levels of serum RBP4 than females . For both genders, serum RBP4 levels in the NAFLD group were significantly higher than in the normal group  [95% confidence interval (CI)]: 1·058 (0·999–1·120)} was a marginally significant variable together with total cholesterol  and HDL cholesterol levels . By contrast, the RBP4 level was not significantly associated with NAFLD in females .Multiple logistic regression analysis was performed using NAFLD as a dependent variable. RBP4 was selected as a significant variable together with the body mass index, HOMA and HDL cholesterol level in all subjects . We alson = 159), RBP4 was found to be positively correlated with body mass index, waist circumference, waist-to-hip ratio, systolic and diastolic blood pressure, total cholesterol, triglycerides, LDL-cholesterol, fasting glucose, HOMA and uric acid levels, but not with body fat  were observed even after adjusting for age, gender, body mass index, HOMA and the presence of NAFLD. We also performed correlation analyses within each gender (P = 0·0136), fasting glucose (P = 0·0018) and HbA1c levels (P = 0·0062) were found to be positively associated with RBP4 after adjusting for age, body mass index and HOMA. In females, only triglyceride levels showed a significantly positive correlation (P = 0·0008) with RBP4 levels after adjusting for age, body mass index and HOMA.In all subjects . When we performed the correlation analysis adjusted for age, gender, HOMA and waist circumference as a marker of abdominal obesity, there were significant correlations between the serum RBP4 levels and the serum ALT and GGT levels .Interestingly, serum RBP4 levels were positively correlated with serum ALT, AST and GGT levels . After aRBP4, a recently identified adipokine, may contribute to systemic insulin resistance.r = 0·3478, P = 0·0049 vs. controls: r = 0·2048, P = 0·0821). These results suggest that a high RBP4 level likely indicates a predictor for NAFLD.Several previous reports including a study of Korean subjectsIt is not yet known whether RBP4 affects lipid metabolism in hepatocytes. A possible explanation is that RBP4 may influence the transactivation of retinoic acid-sensitive transcription factors such as retinoic acid receptor (RAR) and retinoic acid-X receptor (RXR) in NAFLD. RXRs bind to DNA as obligate heterodimers with peroxisome-proliferator activated receptors (PPARs) that regulate the transcription of genes involved in fatty acid metabolism.9et al. found no significant relationship between adipose tissue RBP4 expression and serum RBP4 levels in postmenopausal women,et al. showed that circulating RBP4 was not associated with the amount of visceral and subcutaneous abdominal fat.In rodents, it has been reported that RBP4, normally expressed in liver and hepatocytes, is the principal source of circulating RBP4 under normal conditions and adipose tissue is the organ expressing the second highest level of RBP4·In the multiple logistic regression analysis, the association between NAFLD and RBP4 was observed in all subjects. However, when we analysed within each gender, the RBP4 level was not a significant factor associated with NAFLD in females, and was a marginally significant variable in males. Serum RBP4 levels were higher in male subjects than in females, which is consistent with another Korean study.Limitations of this study include the following. First, we defined NAFLD as a fatty liver based on ultrasonography without histological confirmation. However, we consider ultrasonography to be a reasonable alternative to liver biopsy in relatively healthy subjects. According to a recent review, ultrasound scanning, when positive, can provide a high degree of diagnostic certainty, depending on the prevalence of fatty liver in the population being studied.


Sixty-three patients with extensive-stage small-cell lung cancer were randomized to receive either cyclophosphamide, vincristine, doxorubicin and etoposide (CODE) alone or CODE plus recombinant human granulocyte colony-stimulating factor (rhG-CSF). rhG-CSF administration in support of CODE chemotherapy resulted in increased mean total received dose intensity for all drugs (P = 0.03) with a significant improvement in survival (P = 0.004).


High plasma cortisol levels can cause acute cognitive and neuropsychiatric dysfunction, and have been linked with delirium. CSF cortisol levels more closely reflect brain exposure to cortisol, but there are no studies of CSF cortisol levels in delirium. In this pilot study we acquired CSF specimens at the onset of spinal anaesthesia in patients undergoing hip fracture surgery, and compared CSF and plasma cortisol levels in delirium cases versus controls.Delirium assessments were performed the evening before or on the morning of operation with a standard battery comprising cognitive tests, mental status assessments and the Confusion Assessment Method. CSF and plasma samples were obtained at the onset of the operation and cortisol levels measured. Twenty patients  aged 62 - 93 years were studied. Seven patients were diagnosed with delirium. The mean ages of cases (81.4 (SD 7.2)) and controls (80.5 (SD 8.7)) were not significantly different (p = 0.88). The median (interquartile range) CSF cortisol levels were significantly higher in cases (63.9 (40.4-102.1) nmol/L) than controls (31.4 (21.7-43.3) nmol/L; Mann-Whitney U, p = 0.029). The median (interquartile range) of plasma cortisol was also significantly higher in cases (968.8 (886.2-1394.4) nmol/L, than controls (809.4 (544.0-986.4) nmol/L; Mann Whitney U, p = 0.036).These findings support an association between higher CSF cortisol levels and delirium. This extends previous findings linking higher plasma cortisol and delirium, and suggests that more definitive studies of the relationship between cortisol levels and delirium are now required. Delirium is a severe neuropsychiatric syndrome with core features of acute onset and fluctuating course of inattention. It mainly affects older people, particularly those with chronic cognitive impairment, and is commonly precipitated by acute illness, surgery, trauma or by the effects of drugs . DeliriuSeveral lines of evidence support the hypothesis that high levels of cortisol may play a role in the pathophysiology of delirium ,4. AnimaThere are no published studies which have examined links between cerebrospinal fluid (CSF) cortisol levels and delirium. Determining CSF cortisol levels is potentially important because they provide a more direct and less variable measure of brain cortisol exposure than plasma levels, and because CSF cortisol levels are only variably related to plasma levels . CNS corMore generally, there are very few studies which have examined CSF in delirium -21, despIn the present study we tested the hypothesis that delirium is associated with higher CSF and plasma cortisol levels in older patients with acute hip fracture.We studied patients with acute hip fracture over 60 years old who were awaiting surgery under spinal anaesthesia. Patients gave written, informed consent. Exclusion criteria were residence in an institution, a documented history of dementia or depressive illness, and corticosteroid therapy within the last 10 weeks. The study was approved by the Scotland A Research Ethics Committee.Delirium assessments were performed pre-operatively, no more than 16 hours before the operation, and before any pre-operative sedative medication. Each assessment comprised a standard battery of scales  validated for the diagnosis of delirium . In this125I RIA , with a detection limit of 22.4 nmol/l. CSF cortisol levels were determined with a cortisol ELISA kit . The detection range for this kit is 0.08 - 82.8 nmol/L.Samples of CSF (2 ml) and clotted blood (10 ml) were taken before administration of the spinal anaesthestic agent. Samples were spun at 1000 g for 10 minutes at 4°C. To check for blood contamination in the CSF, the pellet was resuspended in 100 ul phosphate buffer saline followed by a cytospin. All samples were stored at -80°C before analysis. Plasma cortisol assays were performed with a Cortisol-Group differences in cortisol levels were analysed with the Mann-Whitney U test (two-tailed). Non-parametric correlation (Spearman's rho) was used to examine the relationship between CSF and plasma cortisol levels.Twenty-seven patients were recruited. Two did not undergo spinal anaesthesia after recruitment, and an additional patient had their operation postponed. Four further patients were excluded because of blood contamination of the CSF specimens. The age range of the 20 included subjects in the study was 62-93 years . As expected in this group of older hospital inpatients, many had comorbid disease Table . OperatiSeven patients had delirium according to the Confusion Assessment Method. The mean ages of cases (81.4 (SD 7.2)) and controls (80.5 (SD 8.7)) were not significantly different (p = 0.88). Median (interquartile range) CSF cortisol levels were significantly higher in subjects with delirium (63.9 (40.4-102.1) nmol/L) than those without (31.4 (21.7-43.3) nmol/L; Mann-Whitney U, p = 0.029). . The ratios of CSF to plasma cortisol were not statistically different between the groups .The novel finding in this study was that CSF cortisol levels were significantly higher in hip fracture patients with delirium versus controls. Plasma cortisol levels were also significantly higher in cases versus controls. The direction of causation cannot be determined in an observational study, but these findings are consistent with the hypothesis that high brain cortisol levels are associated with delirium.Higher levels of cortisol occurring after hip fracture are an essential part of the systemic response to injury. Consistent with this, the CSF cortisol levels in the present study were generally considerably higher than those in healthy younger control subjects , in healThere is good evidence that the degree of elevation of cortisol, even within the 'stress' range, is important in causing cognitive dysfunction. For example, in healthy young males, high doses of administered cortisol over four days (reaching plasma levels of 700-800 nmol/L) caused verbal memory impairment . Thus, aSome limitations of the study should be noted. The sample size was relatively small. Dementia is a risk factor for delirium and is also associated with higher CSF cortisol levels, and so These results suggest that patients with delirium have higher levels of cortisol in the CSF and plasma. Should a causal role for cortisol be established, this would suggest a potential role for antiglucocorticoid therapies in delirium.HT: hypertension; COPD: chronic obstructive pulmonary disease; IHD: ischaemic heart disease; type 2 DM: type 2 diabetes mellitus.The authors declare that they have no competing interests.AM conceived the study and led its design and coordination. AP, SM, FG and AM carried out the delirium assessments, assays, and contributed to statistical analyses and writing of the manuscript. AdV, TW, IA, RA and JS participated in the design and coordination of the study and contributed to writing the manuscript. All authors read and approved the final manuscript.


The conduct of a qualitative research interview is a complex social interaction that has the potential to influence, or be influenced by, both the researcher and the study participant. When a researcher is identified as a professional nurse, the identification of this role has the potential to influence the researcher-participant interaction. To understand the effect of a nurse-researcher’s involvement in an in-depth interview and on the data collected, issues to address include: clearly identifying the paradigmatic approach in which the research design is situated, examining the study participants' past experiences with research and the researcher’s profession, establishing appropriate boundaries with participants, deciding how to introduce the role of nurse-researcher to the participant and deciding if, or when, it would be appropriate to intervene within the research context. As nurse-researchers, professional knowledge and experiences have the potential to affect relationship development with study participants and obfuscate the purpose of the research interview. It is the researcher’s responsibility to participate in the activity of reflexivity to understand the effect of the nurse-researcher’s involvement on the data and make decisions that protect the participant’s integrity. A nurse working in a clinical context who observes a mother struggling to latch her newborn to the breast, or watches an elderly patient having difficulty getting out of bed or hears an adolescent male express thoughts of suicide would not hesitate to appropriately intervene to support the client. But what if these events were precipitated by a study participant within the context of an interview being conducted by a nurse-researcher for the purpose of data collection in a study? What then would be the roles and responsibilities of the nurse-researcher and what would be the implications of providing nursing care during the process of data collection?Conducting an interview in qualitative research is a complex social interaction that both the researcher and the respondent have the capacity to influence or be influenced by , 2. The In quantitative research, interviews are conducted to complete structured questionnaires. Here the role of the researcher is clear: to remain neutral and objective and to limit researcher influence over the study subject. In contrast to survey research, qualitative interviews are conversational in nature and the goal is to discover how the phenomenon under study is perceived and described by the participant in his or her own words. However, because the qualitative interviewer is the research instrument through which data are collected, filtered and processed, it is his/her values and beliefs that influence what concepts should be further explored , 6. DespThere are anecdotal examples though of qualitative researchers who describe the struggles they experienced in balancing their dual roles as both researcher and clinician. Two physicians, Hamberg and Johansson  discuss It is generally accepted that effective qualitative researchers require strong interviewing skills including the ability to quickly establish rapport during the initial contact . Good raSome authors state that while this trust is necessary to enhance the depth of the information collected, it must be balanced with a certain level of detachment so that partial objectivity can be achieved ,12. ThisThis debate is important because at the foundation of qualitative research there is a continuum of philosophical beliefs, each based on different assumptions. Prior to commencing qualitative interviewing, it is important that nurse-researchers are familiar with the philosophical assumptions underlying qualitative research. Different epistemological assumptions exist about the nature of the researcher-participant relationship in qualitative interviewing. While there is general acknowledgement that qualitative research cannot be purely objective because the research questions, design, and analysis are all influenced by the researcher's experiences, strategies to minimize the influence of the researcher on the interaction have been emphasized , 10. DebProponents of interpretive and critical paradigms reject the possibility that value-free, objective and neutral researcher-participant relationships can be developed within the context of a qualitative interview. They suggest that an openly subjective approach be adopted in qualitative research wherein the researcher participates in the interview as a whole person and strives to develop authenticity through forming a relationship with the participant built on openness, respect and reciprocity , 14. It The role of a qualitative researcher is to collect, analyze and interpret data, and report findings for the purpose of increasing understanding about the phenomenon under study . HoweverNurse-researchers may experience role conflict when deciding how to introduce themselves to participants. Interviewers are aware that the initial introduction will influence the participant's perception of them , 16, 18.An extra layer of complexity exists if the researcher conducts research interviews with his/her own patients. Hamberg and Johansson , family The ability to effectively communicate and interpret data on multiple levels is a skill that contributes to both effective in-depth interviewing and the delivery of professional health care . HoweverA different situation exists when a nurse-researcher decides to intervene or is asked to provide health information during an interview. In a study about the transition to motherhood, Oakley  identifiThe impact of providing clinical interventions during in-depth interviewing can be interpreted differently depending upon the researcher's philosophical assumptions about the nature of the researcher-participant relationship. From a post-positivist perspective, Hutchinson and Wilson  caution In interpretative or critical paradigms the subjective nature of the researcher-participant relationship is highlighted. Therefore, intervening during an interview is seen as enhancing rather than threatening the validity of the data , 26. RatRegardless of the researcher's paradigmatic stance, there are certain circumstances when the clinician has a legal and ethical responsibility to intervene and perhaps even to stop an interview. If a serious conflict should develop, then the need to provide a therapeutic intervention should take precedence over the need to collect data . For exaTo facilitate the implementation of ethical research practices in qualitative research, Hewitt  has deveNo absolute answers can be given to resolve many of the challenges that nurse-researchers experience while conducting qualitative interviews. Instead, researchers need to reflect upon, rather than ignore, the effect of their involvement on the data . ReflexiThere is a considerable amount of literature describing and highlighting the value of reflexivity. Finlay  provides1.In qualitative research it is imperative that the researcher explicitly identifies the paradigmatic approach in which the research design is situated. The assumptions associated with a particular paradigm will define how a researcher interacts with participants. Related questions that need to be raised include: What is the form and nature of reality? What is the nature of the relationship between the nurse-researcher and the participant?2.It is important to explore with the participant their perceptions and experiences with past care from health and social service providers. The participant's perception of the agency sponsoring the research should also be examined. The nature and quality of their previous experiences with staff from that agency also needs to be understood. Particularly in program evaluation studies, if the nurse-researcher is a part of the institution where the participant is receiving care then honest opinions may be suppressed .3.It is impossible to reduce all inequalities of power, but researchers must protect participants' rights to anonymity, confidentiality and reduce any psychological, physical or social risks associated with participating in an interview . To decr4.To minimize role conflict, researchers need to be able to clearly define and articulate their roles to participants. Careful consideration must be given to how one presents him or herself to the participant: is it as a graduate student, researcher or nurse-researcher? The participant's beliefs about the role will influence what information is disclosed . For exa5.The decision to intervene will be determined by the underlying assumptions of the research design and by who identifies the need for intervention and the immediacy of the need. If a life-threatening situation arises, then the nurse- researcher must intervene immediately; other interventions could probably be left until the end of the interview. Sponsoring agencies should be aware that clinician-researchers might provide clinical interventions during an interview. If this is the situation, it is the researcher’s responsibility to be aware of the agency’s policies and procedures, have a method of reporting interventions if necessary and ensure that they have adequate insurance coverage for their professional interventions.If the decision has been made that interventions will not be offered within the interview, then the researcher should be knowledgeable of community resources to which to refer the participant or be able to leave a package of pertinent information with the participant. If there is the potential that the content of the interview will trigger a negative emotional response from the participant, then the researcher has an ethical duty to have a counselor or other services available for follow-up. It would be important to identify if the sponsoring agency has the resources available to respond to an increase in workload in such situations.6.Any decisions to intervene should be documented in the researcher's field notes and described in research publications . AdditioOne of the hallmarks of qualitative interviews is that the interviewer is the research instrument through which data are filtered and processed. This means that it is not only inadvisable but also impossible to have a value-free, impersonal researcher-participant interaction during a research interview. There is a need for continued open and honest discussion about the realities of conducting qualitative interviews by clinician-researchers. Anecdotes in the literature reveal that experienced researchers do struggle with balancing data collection with their role of health care provider and that some do clinically intervene within the context of an interview. Nurses, as part of their educational preparation, develop skills in communication, teaching and counseling and therefore find themselves providing health care to study participants, particularly if the intervention involves health education. In addition, when these skills are appropriately incorporated into a qualitative interview the result is the development of a more meaningful relationship with the participant.


Live kidney donation is an excellent way of increasing the donor pool. The introduction of the laparoscopic donor nephrectomy has resulted in an increase in live organ donation in the western hemisphere. There is no data on its impact on organ donation in India. However attractive as it may seem, the procedure is associated with a definite learning curve and does compromise donor safety. The procedure is also expensive in terms of the equipment required. The mini-donor nephrectomy is an excellent alternative, has no learning curve and is ideally suited for donors in India who have a low BMI. The procedure is also relatively inexpensive. We are in need of a donor registry rather than reports from single institutions to fully evaluate the risks and benefits of both procedures. Live donor transplantation provides a significant advantage when compared with cadaveric renal transplantation in terms of improved patient and graft survival. With excellent one and five-year graft survivals, the disparity between demand and supply has grown. Most transplant units have looked at their live donors to increase the supply of organs. The driving force for live related renal donation has been an excellent track record of donor safety and the optimal quality of the organ that has been procured.The major disincentive to live renal donation organ is the length of hospital stay, postoperative pain and the time taken to get back to full activity. LaparoscThere is little doubt that there is significant scope for improvement with the conventional muscle cutting rib resecting incision, which leads to considerable pain and muscle weakness resulting in a bulge in the postoperative period. Both laparoscopic and the mini-donor nephrectomy are effective alternatives. Laparoscopic donor nephrectomy represents a significant surgical advance for the live renal donor. It is associated with a smaller scar-less postoperative pain and quicker recovery. Most donors are able to get back to their original jobs within two weeks.–3 The suA review of the existing literature reveals that the subject of live donor nephrectomy is a seat of under-reporting and under estimation of complication. The advent of the laparoscopic donor nephrectomy has resulted in most centers in India critically evaluating the service that they offer their living donors. It is important to remember that the donor nephrectomy has two vital components the safety of the donor and the optimal condition of the organ being harvested. The flank approach to donor nephrectomy has stood the test of time with regards to both .The operation is safe and provides a good quality organ. However, it is associated with significant morbidity in terms of loin pain, structural disability and cosmesis, which may occur in 7 to 9% of patients.et al.[[56]In a study by Shaffer et al. of 201co[64]There is little or no data on its impact in transplantation in India. Laparoscopic donor nephrectomy is associated with a learning curve and is associated initially with significant morbidity. In terms of donor safety in laparoscopic donor nephrectomy at least nine peri-operative deaths have been reported with and at least 15 graft losses directly related to the surgical technique of laparoscopic donor nephrectomy were found.In India, cadaver organ donation accounts for an insignificant number of renal donations. Almost all donations are from live donors. These are either related in the vast majority of cases or authorized as per the Human Organ Transplant Act. The commonest donor is usually the female sex and is usually the mother, wife or sister. Most of these donations are to bread winners of the family to whom the entire economic survival of the family is linked to. Also, vast majority of these donors are unemployed. For them, the most important factor is the quality of organ harvested and the quality of life that recipient enjoys to make him the bread winner again.The pneumo-peritoneum that is created during laparoscopic donor nephrectomy may be detrimental on both pulmonary function and vascular perfusion. The incrThe live donor is sacred to the renal transplant program. Most open donor programs leave the better functioning kidney behind. This has resulted in the right kidney being harvested in approximately 22% to 35% of patients. The right kidney is more difficult to harvest laparoscopically and this has resulted in the right kidney being harvested in only 2% to 5% of donors. LaparoscMost centers that embarked on a laparoscopic donor nephrectomy program reported on an initial incidence of urological complications to be as high as 10.5%. In open donor nephrectomy, the complications are less than 2%. In laparoscopy, this incidence has declined with increasing experience and appreciation of the fact that the gonadal vein should be harvested with the ureter.The economic considerations in laparoscopic donor nephrectomy can be considerable. In the western hemisphere the cost of disposables required for laparoscopic surgery is $2251 as compared to $812 for an open donor nephrectomy. The big The issue of securing the pedicle in a laparoscopic donor nephrectomy has aroused considerable controversy. There are at least two reports in literature of hem-o-lock clips slipping in the donor leading to exsanguinating hemorrhage.  It is noAt our center, we have explored mini-donor nephrectomy and laparoscopic donor nephrectomy as an option for our live related renal donors. The mini donor nephrectomy procedure consists of a non rib resecting flank incision above the eleventh rib which is extended depending upon the position of the kidney. The ureter is mobilized with the gonadal vein and the artery and nein are dissected. Two narrow based retractors are used and the artery and vein are ligated. The incision is closed inlayers with 4-0 monocryl applied to the skin.Our initial results on 78 donors with a mean age of 40.98 years and a mean weight of 63.66 Kg revealed an incision length of 9.2 cm and a time to harvest of 45.15 minutes. The mean post-operative stay was 2.26 days and no kidney was lost nor any major complication encountered in the donor.  We commeSixty consecutive donors were randomized into two groups. Group 1 underwent a laparoscopic donor nephrectomy while group II underwent an open donor nephrectomy. Laparoscopic donor nephrectomy was carried out using a standard four port approach and the kidney was removed manually. The technique of the mini-donor nephrectomy has already been described.Both groups were evaluated with regard to operative time, postoperative stay and the visual analogue pain score at the time of discharge. The graft function was also evaluated at one month. Both groups were also evaluated to the resumption of normal diet and the BMI also noted .No graft or donor morbidity occurred in either group. Ileus was a significant problem in the laparoscopic group and this lead to a significant number of donors complaining of discomfort and pain in the post –operative period. It was primarily because of this discomfort and ileus that the laparoscopic group had a longer postoperative stay then the mini-donor group. We thus concluded that in our setting where most of the donors have a low BMI the mini-donor nephrectomy may be a more viable option in terms of donor safety, economics and recovery.et al. in a recent meta analysis comparing laparoscopic versus open donor nephrectomy evaluated seventy three studies and concluded that though open donor nephrectomy was associated with a shorter post-operative and warm ischemia times patients undergoing laparoscopic donor nephrectomy may benefit from a shorter hospital stay and faster return to work without compromising graft function.Nanidiset al. inet al. [In another recent article comparing the mini-incision muscle splitting (MIDN) open approach to the laparoscopic donor nephrectomy (LDN) Kok et al.  found thLaparoscopic donor nephrectomy remains a procedure in evolution. The high costs and the training required have been major deterrents to its widespread use in India. We are in need of a live organ donor registry to determine the combined experience of complications and long term outcomes, rather than short term reports from single institutions. However, with requisite training it remains an attractive alternative for renal donation.


Renal transplantation is the treatment of choice for a suitable patient with end stage renal disease. Unfortunately, the supply of donor organs is greatly exceeded by demand. In many countries the use of kidneys from living donors has been widely adopted as a partial solution. Traditionally donor nephrectomy has been performed via a open flank incision however with some morbidity like pain and a loin scar. Currently, the donor nephrectomy is increasingly being performed laparoscopically with the objective of reducing the morbidity. It is also hoped that this will lead to increasing acceptance of living donation. The first minimally invasive living donor nephrectomy was carried out in 1995 at the Johns Hopkins Medical Center and since then many centers have undertaken laparoscopic living donor nephrectomy. The laparoscopic approach substantially reduces the donor morbidity and wound related problems associated with open nephrectomy. The laparoscopic techniques thus have the potential to increase the number of living kidney donors. The present article attempts to review the safety and efficacy of transperitoneal laparoscopic donor nephrectomy. End stage renal disease (ESRD) patients have the option of lifelong maintenance hemodialysis, continuous ambulatory peritoneal dialysis (CAPD) or kidney transplantation and of these, kidney transplantation is the treatment of choice for a suitable patient. Unfortun6Laparoscopic live donor nephrectomy (LLDN) can be done transperitoneally or retroperitoneally on either side. The operative technique of LLDN has undergone many refinements since it was first described. The approach is most commonly transperitoneal, which allows adequate working space and easy dissection.The donor is placed in a modified lateral decubitus position. Pneumoperitoneum is created by insufflation of carbon dioxide using a veress needle or after introduction of a laparoscopic 12 mm port at the umbilicus by open Hassan technique. The umbilical port is primarily used as a camera port. Another 12 mm laparoscopic port is placed between the umbilical port and anterior superior iliac spine . A 5 mm port is placed in line with the camera port about 3c A fourth 5 mm laparoscopic port may be used for retraction, if needed and is placed 4 cm below the costal margin in the anterior axillary line.The lateral peritoneal reflection is incised along the line of Toldt from the splenic flexure to the pelvic inlet and dissection is continued in the plane between Gerota's fascia and descending colonic mesentry. The left gonadal vein is followed up to the left renal vein. Before beginning the hilar dissection 25 mg of mannitol is administered. At least 3–4L of fluid is given during surgery to negate the effect of pneumoperitoneum. The adre10By placing forceps between previously mobilized renal artery and vein, excellent exposure of renal hilum is possible. The renal artery and vein are sequentially ligated with a GI vascular stapler or 13 mm Weck Clips . The kidney is then carefully extracted from the pfannenstiel incision.The transperitoneal laparoscopic approach may be similar to that on the left side. Modifications have been made in right LLDN to compensate for shorter vessels and to prevent thrombotic complications. In the recipient, the iliac vein is completely mobilized by dividing all of its posterior branches to facilitate making a tension-free anastomosis. The dissInsertion of an Endo-GIA stapler through the port positioned in the right lower abdominal quadrant allows control of the renal vein at its junction with the vena cava, preserving the maximum possible length of renal vein. To maximHowever, with increasing experience more and more donors can be taken up for left transperitoneal approach as multiple vessels and other vascular anomalies are no more a contraindication for this procedure.At many centers, the number of individuals willing to undergo LLDN today would not have donated a kidney if open surgery was the only option available for organ donation. This is so because LLDN offers decreased postoperative pain, marked cosmetic benefit and better convalescence compared to open donor nephrectomy.P < 0.05) in LDN series compared with open donor nephrectomy series.[In most reported experiences, the operating time at the beginning of the LDN learning curve was generally longer than for open live donor nephrectomy. In a mety series. However,y series. Our meany series..Laparoscopic live donor nephrectomy and open donor nephrectomy are comparable in the estimated blood loss and postoperative transfusion requirement.–23 In faThe reported frequency of open conversion during LDN ranges from 0 to 13%. The mostet al.[P < 0.05). Similar results have been found in other series[Reduced postoperative pain and recuperative time, the major advantages of LDN, have been demonstrated in several studies. Ratner et al. concludeer series [Table 4Comparing LDN to open living donor nephrectomy (OLDN), the hospital stay, resumption of oral intake, the time to return home have been found to be significantly favorable to the LDN group2627 Tab26.Several series have addressed donor quality of life following LDN and ODN. It has been shown that LDN resulted in a shorter time until patients were able to drive, take care of the home and return to full activity, work and regular exercise.27 In theet al. (3.3 min in the first 25 LDN cases versus 1.8 min in the most recent 25 LDNs (P< 0.001).[et al.[et al., where the rate of decline in serum creatinine concentration, S Cr. in the first 10 days, changes in S Cr. at three months, acute rejection rate, biopsy-proven chronic allograft rejection and graft survival were assessed according to the duration of WIT.[The warm ischemia time (WIT) presents a major concern as it has always been slightly longer in the laparoscopic group when compared with open donor nephrectomy due to the longer extraction time. It has been thought that any increase in this would translate into a poor graft function. This notion has been disproved by various studies suggesting no bearing of this small difference on the recipient outcome. The warm ischemia time during LDN may range between 95 and 300 seconds.21 At the< 0.001). A simila).[et al. The effen of WIT. AnalysisWe evaluated the impact of warm ischemia time in LDN. It did not correlate with the incidence of delayed graft function, acute rejection or allograft or recipient survival .et al. confirmed no significant difference in serum creatinine level in LDN versus open donor nephrectomy group .[Several clinical trials have shown no significant difference in the serum creatinine level between open and LDN at three days, 30 days and three months after transplantation. At a folP =0.26).P = 0.9) and the graft survival rate  has also been similar.[In a comparison between open donor nephrectomy and LDN in patients with multiple renal arteries, the postoperative serum creatinine level after one year of follow-up has been found to be similar  and left renal artery length (P = 0.38), right renal vein (P= 0.38) and artery length (P= 0.33) were similar. Ureteric length was significantly greater in the LDN group for both left and right nephrectomy. This study demonstrated that LDN yielded kidneys that were structurally and functionally equivalent to those acquired by the open operation.There have been concerns about vessel and ureteral length which could be harvested in LDN as it would have a direct bearing on the recipient operation. In a randomized controlled trial studyinget al. to reduce an initial 9.1% incidence of ureteral complications in the first 110 cases to 3% in the last 100 cases.[In initial LDN series, ureteral injuries occurred more frequently than during open donor nephrectomy . Subseque00 cases. The Univ00 cases. [Table 2A systematic review of reported LDN series found no significant differences between the rate of acute rejection after LDN (2–30%) and open donor nephrectomy (0–32%). Similar et al. reported a higher operating cost in LDN series (73% greater) compared with open donor nephrectomy.[Wolf hrectomy. However,hrectomy. PresentlLaparoscopic donor nephrectomy has now been established as a safe and efficacious procedure, especially with refinements in equipment and surgical techniques. It provides all the benefits of minimal invasive surgery to the most unique patient that is the donor while maintaining results equivalent to the ODN in terms of graft function and recipient outcome. Making modifications in the original procedure can significantly bring down the cost, thus making it a procedure of choice for developing nations.


We therefore studied the effects of adult human leptomeningeal CSF on the behaviour of adult human NSCs (ahNSCs).Neural stem cells (NSCs) are a promising source for cell replacement therapies for neurological diseases. Growing evidence suggests an important role of cerebrospinal fluid (CSF) not only on neuroectodermal cells during brain development but also on the survival, proliferation and fate specification of NSCs in the adult brain. Existing + astroglial cells compared to differentiation in standard culture media and a lower number of β-tubulin III+ neuronal cells.Adult CSF increased the survival rate of adult human NSCs compared to standard serum free culture media during both stem cell maintenance and differentiation. The presence of CSF promoted differentiation of NSCs leading to a faster loss of their self-renewal capacity as it is measured by the proliferation markers Ki67 and BrdU and stronger cell extension outgrowth with longer and more cell extensions per cell. After differentiation in CSF, we found a larger number of GFAPin vitro a strong glial differentiation stimulus and leads to a rapid loss of stem cell potential.Our data demonstrate that adult human leptomeningeal CSF creates a beneficial environment for the survival and differentiation of adult human NSCs. Adult CSF is  Neurospheres are either multicellular aggregates or clones originating from one single cell depending on the cell density [Neural stem cells (NSCs) are a promising source for cell replacement therapies in the brain and the spinal cord . It is c density ,9,11,15. density -20. In t density -20.+, immature neurons, has been detected compared to standard culture media, indicating a positive influence of embryonic avian CSF on neurogenesis. As there are well known differences between avian and mammalian CSF [in vivo [in vitro cell system of adult human NSCs in culture as a model to investigate the effects of adult human CSF on NSC behaviour.Investigations examining the influence of CSF and its contents on survival, proliferation and differentiation of NSCs were so far mostly performed with embryonic avian CSF -23. In tlian CSF  with a m[in vivo -23,25-27in vitro expansion for at least three passages in standard media, NSCs were transferred to uncoated chamber slides and expanded in standard expansion medium or CSF for additional 72 h. Thereafter, cells were stained with Hoechst 33342 and propidiumiodid to determine the amount of necrotic cells. Our results showed a significantly higher survival rate of NSCs in CSF compared to standard expansion medium  with 6.9 ± 1.9% of necrotic cells in CSF versus 46.0 ± 12.9% in expansion medium . After 72 h, the proportion was 22.7 ± 7.5% versus 6.5 ± 0.8% for standard media versus CSF, respectively  and 72 h (BrdU) after media was changed. At each time point, the percentage of Ki67+ and BrdU+ NSCs was significantly higher in expansion medium compared to the one in CSF, representing a larger number of proliferating cells in expansion media. Hence, after 24 h Ki67 was detected in 20.4 ± 7.3% of NSCs expanded in standard medium compared to only 0.2 ± 0.01% of NSCs expanded in CSF  as in P4-8F . The low percentage of MAP2+ cells in standard media and CSF is most likely caused by the lack of fully differentiated phenotypes, as MAP2 represents a marker for mature neurons. Staining against the neuronal marker protein β-tubulin III, a marker for immature neurons, revealed 8.7 ± 3.6% β-tubulin III+ cells in CSF compared to 30.7 ± 8.4 β-tubulin III+ cells in standard media (P = 0.014).To investigate the question whether the presence of adult human leptomeningeal CSF does have an influence on astrogliogenesis, oligodendrogenesis or neurogenesis, adult NSCs were allowed to differentiate for 7 days on PLL-coated chamber slides in either standard differentiation media or CSF. After differentiation in standard media, 24.7 ± 1.7% of the cells were GFAPin vitro model to study the effects of adult leptomeningeal CSF on NSC behaviour including survival, self renewal and differentiation. The central finding of our study is that in vitro, adult CSF promotes survival and differentiation of ahNSCs, but drives the differentiation process towards astrogliogenesis. In accordance with these findings, the loss of stem cell potential is accelerated when cultured in adult CSF. These findings suggest that adult CSF contains key factors involved in the control of cellular proliferation and differentiation processes. This assumption is supported by in vivo findings, demonstrating that adult NSCs of the subventricular zone have transitory contact with the ventricular brain cavity and many of them still posses one microcilia which extends into the CSF [There is growing evidence that CSF plays an important role in physiological as well as pathophysiological processes of the brain including adult neurogenesis -30. In a the CSF -35. In a the CSF -23 that in vivo [Based on the knowledge of embryonic CSF studies, it has already been postulated that diffusible factors in embryonic CSF regulate the three basic cellular behavioural parameters of neuroephitelial stem cells and that embryonic CSF may play a key role in brain development in vivo .However, how CSF influences neuroectodermal cells during development remains enigmatic, but the components contained in CSF as well as CSF pressure and flow seem to play an important role ,36. Regain vivo studies, investigating for example the behaviour of fetal NSCs after injection in the fourth ventricle of spinal cord lesioned rats with a good survival of grafted cells within the CSF [in vitro study of our own group with fetal rat NSCs [+ in CSF. In standard culture media, 31% of the cells were β-tubulin III+. Therefore, our data strongly suggest inhibitory effects of CSF on neurogenesis of ahNSCs, but promoting effects on astroliogenesis. Possible factors in CSF influencing differentiation behaviour of NSCs are bone morphogenetic proteins (BMPs): Monoclonal antibodies against BMP7 were for example shown to inhibit CSF induced dendritic outgrowth of neurons. BMP4 was shown to induce neuronal differentiation of NSCs by activating the ERK and inhibiting the GSK3β pathway. Both described effects could be blocked by Noggin, a BMP inhibitor [CSF as a beneficial environment for cell survival and growth has also been postulated by  the CSF ,39, as wrat NSCs . In the nhibitor ,41. ThesIt is well accepted that lumbar CSF is different from ventricular CSF because of both passive diffusion processes across the blood-CSF-barrier and suggested active secretion processes during the cranio-caudal circulation . ConsistTogether, our results demonstrate that adult leptomeningeal CSF has a trophic influence on adult human NSCs: survival and differentiation into astroglial cells are promoted. Thus, our data point to a pivotal role of CSF in regulating adult neurogenesis under physiological and presumably also under pathological conditions as suggested previously -30. Futu-3, normal immunoglobulin quotients: IgG 2.1 × 10-3, IgA 1.1 × 10-3, IgM <0.2 × 10-3. Pooled CSF samples were aliquoted and frozen at -80° until used.The CSF samples were taken for diagnostic purpose from adult patients in the Neurological Clinic of the Ernst Moritz Arndt University of Greifswald by a lumbar puncture. Scientific use of CSF samples was approved by the local Ethics Committee. All patients gave a written informed consent for the diagnostic procedure. Lumbar puncture was performed by standard protocols. The final diagnosis of all patients was Idiopathic Normal Pressure Hydrocephalus (NPH). CSF was only used if all standard parameters were normal . Contamination with blood was excluded. In all patients, tumors and infectious diseases were excluded. Surplus CSF from diagnostic samples of all patients was spun down to remove remaining cells, pooled and analyzed to exclude non-sterility and presence of inflammatory markers. The pooled CSF was normal in all standard parameters; contamination with blood was excluded once again. The exact parameters were as follows: Cell count <1/μl, no blood contamination, normal protein of 369 mg/l, normal glucose of 3.6 mmol/l, normal lactate of 2.0 mmol/l, normal ferritine of 7.2 μg/l, normal albumin quotient of 5.0 × 102 conditions of 5% CO2, 92% N2 and 3 ± 2% O2. Fresh medium was added once a week, growth factors twice a week. For BrdU labelling, cells were incubated with 10 μm BrdU for 72 h. For immunocytochemistry studies of neurospheres, these were allowed to attach for 2-4 h before been fixed as described below.Adult human hippocampal tissue was obtained from routine epilepsy surgery procedures  following informed consent of the patients. All procedures were in accordance with the Helsinki convention and approved by the ethics committees at the EMA University of Greifswald (III UV 77/06) and at Dresden University of Technology (EK47032006). The tissue was stored in ice-cold Hank's balanced salt solution (HBSS) supplemented with 11 mM glucose and 1% penicillin/streptomycin. In all patients, tumours and infectious diseases were excluded by means of high-resolution magnetic resonance imaging and screening for inflammatory markers. Additionally, neuropathological tissue examination did not reveal evidence for tumour formation. For expansion of neurospheres, tissue samples were dissociated using trypsin, DNase and mechanical trituration similar as described previously . SeveralCells were differentiated by plating them onto poly-L-lysine-coated chamber slides or 6-well-plates in P4-8F  or in CSF without adding any growth factors. Some of the differentiation experiments were conducted in the presence of 150 ng/ml recombinant Noggin . For studying cell survival, proliferation and neurite outgrowth cells were allowed to differentiate for up to 72 hours, for investigating cell fate decisions for up to 7 days respectively. Half of the media was changed every third day. For investigating cell morphology, survival rate and marker expression by immunocytochemistry, the cultures were fixed from 0 h up to 72 h and 14 days after starting the differentiation process.For immunocytochemistry, cell cultures were fixed in 4% paraformaldehyde in PBS or with 4% paraformaldehyde/PBS followed by ice-cold acidic ethanol and 2N HCL for BrdU staining. Immuncytochemistry was carried out using standard protocols. Cell nuclei were counter stained with 4,6-diamidino-2-phenylindole (DAPI). To determine the self renewing potential of NPCs, Ki67 expression and BrdU incorporation were used. Ki67 is detected in the nucleus of proliferating cells in all active phases of the cell cycle from the late G1 phase though the M-phase ,44. BrdUFor determining the survival rate during expansion and differentiation, dead cells were stained with propidiumiodid (PI) 1:50 , cell nuclei were counter stained with Hoechst 33342 1:1000 . Images were captured using inverse fluorescence microscopes .2 where appropriate. Neurite lengths were measured with a semi-automatic distance measurement computer program (VisRoute®). In a typical experiment, a total number of 500 to 1,000 cells were counted per marker, and 500 to 1,000 neurites per time point were measured. The mean values of ≥ 3 experiments for each condition are given together with standard deviations. Statistical comparisons were made by ANOVA with post-hoc t-test or Dunnett's t-test where appropriate. P-values < 0.05 were considered as statistically significantFor quantification of the percentage of cells expressing a given marker, the number of positive cells of at least five representative areas per experiment was determined relative to the total number of DAPI/Hoechst-labelled nuclei, or field of view in cmThe authors declare that they have no competing interests.JB carried out the experiments and drafted the manuscript. MK and AH participated in part of the experiments. AH helped optimizing the culture conditions. AD provided the CSF samples and supervised the quality control in the CSF laboratory and contributed to the initial study design. HS and MK performed the surgical procedures and provided the tissue samples. UR selected the appropriate patients for the surgical procedures. MS planned the experiments and performed the design and coordination of the study. JB, MS and AS performed the discussion of the study. MS and AS finalized the manuscript. All authors read and approved the final manuscript.


Sporadic cases have developed pulmonary toxicity after receiving chemotherapy and granulocyte colony-stimulating factor (G-CSF). However, because such cases received chemotherapy that alone frequently causes pulmonary toxicity, the role of G-CSF in this toxicity has been unclear. CHOP therapy  only slightly induces pulmonary toxicity. However, we observed a considerable incidence of this toxicity in non-Hodgkin's lymphoma subjects receiving CHOP therapy and G-CSF . In this cohort, among various characteristics, including the dose and interval of CHOP therapy, only the mean peak leucocyte count (MPLC) with each therapy cycle was associated with development of this toxicity (MPLC > or = 23.0 x 10(9) l(-1), 6 out of 29 cases; MPLC < 23.0 x 10(9) l(-1), 0 out of 23 cases; P = 0.020). These findings suggest that the effect of G-CSF is the main determinant of the pulmonary toxicity in these cases. Because the toxicity was associated with a large MPLC and did not recur in cases readministered G-CSF, an idiosyncratic reaction to G-CSF is unlikely to be the pathogenesis of this toxicity. Thus, lowering the G-CSF dose seems to be useful in the prevention of this toxicity. In all six cases, the time course of manifestation of the toxicity was the same, and early application of high-dose corticosteroid led to cure. This knowledge will be helpful in the care of similar cases.


Granulocyte colony-stimulation factor (G-CSF) is a cytokine that selectively promotes growth and maturation of neutrophils and may modulate the cytokine response to inflammatory stimuli. The purpose of this study was to examine the effect of G-CSF on ex vivo peripheral blood mononuclear cell (PBMC) functions. Ten patients with breast cancer were included in a clinical trial in which r-metHuG-CSF was administrered daily for 5 days to mobilize peripheral blood stem cells. Ten healthy women were also included as controls. Our data show that G-CSF treatment induces an increase in peripheral blood leucocyte, neutrophil, lymphocyte and monocyte counts. We have found a modulation in the percentages of CD19+, CD45+CD14+, CD4+CD45RA+ and CD4+CD45RO+ cells in PBMC fractions during G-CSF treatment. We have also found a significant reduction in the proliferative response of PBMC to mitogenic stimulation that reverted 14 days after the fifth and the last dose of G-CSF. Furthermore, it was not associated with significant changes in the pattern of cytokine production. The mechanism of this immunoregulatory effect is probably indirect since G-CSF receptor has not been found in T lymphocytes. This mechanism and its potential clinical applications remain to be elucidated. © 1999 Cancer Research Campaign


The hematopoietic Granulocyte-Colony Stimulating Factor (G-CSF) plays a crucial role in controlling the number of neutrophil progenitor cells. Its function is mediated via the G-CSF receptor, which was recently found to be expressed also in the central nervous system. In addition, G-CSF provided neuroprotection in models of neuronal cell death. Here we used the retinal ganglion cell (RGC) axotomy model to compare effects of local and systemic application of neuroprotective molecules.G-CSF receptor is robustly expressed by RGCs in vivo and in vitro. We thus evaluated G-CSF as a neuroprotectant for RGCs and found a dose-dependent neuroprotective effect of G-CSF on axotomized RGCs when given subcutaneously. As stem stell mobilization had previously been discussed as a possible contributor to the neuroprotective effects of G-CSF, we compared the local treatment of RGCs by injection of G-CSF into the vitreous body with systemic delivery by subcutaneous application. Both routes of application reduced retinal ganglion cell death to a comparable extent. Moreover, G-CSF enhanced the survival of immunopurified RGCs in vitro.We found that the We thus show that G-CSF neuroprotection is at least partially independent of potential systemic effects and provide further evidence that the clinically applicable G-CSF could become a treatment option for both neurodegenerative diseases and glaucoma. Granulocyte-Colony Stimulating Factor (G-CSF) promotes the survival, differentiation and proliferation of cells of the neutrophilic lineage ,2. It beIn analogy to its anti-apoptotic effect in the hematopoietic system, G-CSF was recently found to reduce infarct volume and to improve functional recovery in rodent studies of acute and subacute stroke ,9-18. Coin vivo models for neurodegeneration, death of axotomized RGCs fulfils all criteria of apoptosis  the following primers were used: ratGCSFR-frag32s (CCATTGTCCATCTTGGGGATC) and rat-GCSFR-frag265as (CCTGGAAGCTGTTGTTCCATG) with an expected product length of 233 bp. Cycling conditions were as follows: 5 minutes at 94°C (only first cycle); 30 seconds at 94°C, 1 min at 66°C, 40 seconds at 72°C for 50 cycles; final elongation for 5 min at 72°.RNA was prepared from primary RGCs by Qiagen RNA-Easy columns. Reverse transcription was performed using oligo dT primers and Transcriptor reverse transcriptase (Roche). For detection of the G-CSF receptor [GenBank: Data were expressed as the mean ± SEM. Statistical significance was assessed applying one-way ANOVA followed by the Bonferroni's post hoc test .TF performed cell counting, immunocytochemistry, RT-PCR, interpretation of results and prepared the figures and drafted the manuscript. JCMS performed cell counting and immunohistochemistry and drafted the manuscript. BG was responsible for surgery of rats. KM helped with immunohistochemistry and surgery. GR prepared RGC cultures. GPHD helped with RGC culture and data mining. MB and AS contributed to the experimental design and helped to draft the manuscript. JHW had the idea for the project, outlined the experimental design, interpreted results and helped with manuscript writing. He was also responsible for surgery, cell counting and immunohistochemistry. All authors read and approved the final manuscript.


This study aimed to evaluate the prevalence and predictors of AIDS-related complicated cryptococcal meningitis. The outcome was complicated cryptococcal meningitis: prolonged (≥ 14 days) altered mental status, persistent (≥ 14 days) focal neurologic findings, cerebrospinal fluid (CSF) shunt placement or death. Predictor variable operating characteristics were estimated using receiver operating characteristic curve (ROC) analysis. Multivariate analysis identified independent predictors of the outcome.2 serum and CSF CRAG titers to predict complicated forms of cryptococcal meningitis were comparable, 0.78 (95%CI: 0.66 to 0.90) vs. 0.78 (95% CI: 0.67 to 0.89), respectively . The ROC areas to predict the outcomes were similar for CSF pressure and CSF CRAG titers. In a multiple logistic regression model, the following were significant predictors of the outcome: baseline focal neurologic findings, head CT abnormalities and log2 CSF CRAG titer.From 1990-2009, 82 patients with first episode of cryptococcal meningitis were identified. Of these, 14 (17%) met criteria for complicated forms of cryptococcal meningitis . Patients with complicated cryptococcal meningitis had higher frequency of baseline focal neurological findings, head computed tomography (CT) abnormalities, mean CSF opening pressure, and cryptococcal antigen (CRAG) titers in serum and CSF. ROC area of logDuring initial clinical evaluation, a focal neurologic exam, abnormal head CT and large cryptococcal burden measured by CRAG titer are associated with the outcome of complicated cryptococcal meningitis following 2 weeks from antifungal therapy initiation. Cryptococcal meningitis remains one of the leading causes of morbidity and mortality in patients with AIDS in resource limited settings . Up to tThis retrospective case series of HIV-infected adults experiencing a first episode of cryptococcal meningitis was approved by the UCSD Human Research Protection Program (project# 071931) and performed at UCSD Medical Center. All patients provided written informed consent for the collection of samples and subsequent analysis. This study was conducted according to the principles expressed in the Declaration of Helsinki.Patients needed to be either antiretroviral naive or, if not naive, off antiretrovirals for at least eight weeks prior to diagnosis of cryptococcal meningitis. Patients needed to be off fluconazole or other systemic antifungals at least eight weeks prior to diagnosis of cryptococcal meningitis. Baseline characteristics included epidemiological, clinical, serological, microbiological and radiologic data for each patient collected within 48 hours of admission. Serum and CSF CRAG titers were obtained concurrently at the time of first lumbar puncture. Three reviewers independently completed case study forms for each patient . In case of data disagreement, reconciliation was performed by two independent reviewers (J.C & A.M.S.).20 has been reported in normal asymptomatic individuals in the general population , CSF opening pressure ≥ 30 cm HThe present study to assess AIDS patients at risk for complicated forms of cryptococcal meningitis found that: (1) focal neurologic deficit, CT imaging abnormality, and CSF CRAG at the time of initial hospital evaluation independently predict the outcome of complicated forms of cryptococcal meningitis following two weeks from antifungal therapy.;(2) Serum and CSF CRAG as measures of fungal burden were comparable in their ability to discriminate between those with and without outcome; (3) CSF CRAG and initial opening pressure were comparable in ROC discrimination and (4) CRAG (both serum and CSF) was moderately correlated with initial CSF opening pressure.AIDS related cryptococcal meningitis (in the absence of immune reconstitution) is often clinically characterized by a massive fungal burden with minimal CSF pleocytosis but with elevated CSF pressure ,7. Intra20 was associated with complicated forms of cryptococcal meningitis in bivariate analysis, it was not significant in multivariate analysis. Nonetheless, the severity of intracranial hypertension at baseline has been associated with fatal outcomes within two weeks of initiation of therapy in some studies [20. We also note that in our cohort almost thirty percent of patients who developed a complicated course had no focal neurologic findings and only minimal central nervous system referable symptoms at time of presentation.Although, having a baseline CSF opening pressure ≥ 30 cmH studies , but not studies . This di studies ; and (3) studies . We acknDeath is not the only relevant outcome of this opportunistic infection . Our defThis was an observational retrospective study and important limitations need to be recognized. First, fourteen patients had no baseline opening CSF pressure measurement. Among those who had no CSF pressure documented, all but one had an uncomplicated course. The main reasons for missing CSF pressure documentation included: technical challenges that arose during lumbar puncture while performed in the emergency room and the illness episode occurred between 1990 and 1995 when routine measurement of CSF opening pressure was not as widely accepted as currently. Second, certain variables (Table In summary, a focal neurologic exam, abnormal head CT, and large cryptococcal burden measured by CRAG assessed within 48 hours of admission are associated with the outcome of complicated forms of cryptococcal meningitis assessed 2 weeks from antifungal therapy initiation. These findings underscore the importance of quantitative CRAG testing in AIDS patients with suspected cryptococcal meningitis, particularly in resource limited settings where the burden of cryptococcal meningitis is high and access to this technology is limited.The authors declare that they have no competing interests.ERC carried out study design, data collection, statistical analysis and draft manuscript. HJ and SK performed data collection and filled case report forms. JC and AMS, carried out data reconciliation by chart reviews. WCM participated in every single step of study from conception, design, statistical analysis and drafting of manuscript. All authors review and approved final version of manuscript.


Marginal donors are now accepted by many centers for kidney transplantation. We report a case of procurement of  Definition of brain death and use of organs for purpose of transplantation was accepted in India in 1994. The Government of Gujarat had accepted the law in 1997 and we had performed the first deceased donor transplantation in the same year. In 2006, we had established intercity cadaver transplant program and procured organs from remote cities.en bloc to an adult recipient. Procurement of organs was performed in a city 270 km away from our center.Organ procurement for purpose of transplantation from deceased pediatric donors is rare in India. We report a case of procurement of both kidneys from a four and half year old child and transplantation in situ after procurement by clamping the suprarenal aorta using Ringer's lactate solution [en bloc for transport and transplantation. On bench, the laceration was repaired by Surgicel® bolster and upper end of aorta and vena cava were sutured by 4/0 and 5/0 polypropylene sutures respectively [A 5-year-old boy had met with road traffic accident and was declared brain dead. Parents and other nearby relatives gave consent for use of organs for purpose of transplantation. The size of both kidneys on ultrasound examination was 7.8 × 2.5 cm. A 1.2 cm long grade 1 injury was found on the anterior surface of the right kidney. Kidneys were perfused solution  and packectively . The lowectively . Both ur2.The cold ischemic time was 11 h and 30 min and re-warming time was 35 min. Drain tube was removed after 48 h of surgery. Urine output was established promptly and patient had serum creatinine value of 0.90 mg/dl at the time of discharge on fifteenth post operative day. Antithymocyte globulin, Rituximab and methyl prednisolone were given as induction agents and she was maintained on cyclosporine, mycophenolate mofetil and prednisolone. During follow-up after 2 years and 5 months post-transplant, her serum creatinine value is 0.99 mg/dl with normal blood flow pattern on doppler ultrasound examination and each kidney size is 11 × 4.5 cm. She does not have proteinuria or hypertension. The estimated GFR was 88 ml/min/1.73 men bloc transplantation of kidneys from young deceased donor is controversial. Single kidney transplantation is more likely associated with technical complications and long term graft loss due to hyperfiltration injury to the graft. To overcome such problems, en bloc transplantation is carried out.[en bloc kidneys from a pediatric donor.[Single kidney versus ried out. More recic donor. Injury tKidneys from small donors may be an increased risk for late graft failure if they are transplanted into large recipients, and therefore, the relative size of the donor and recipient should be taken into account. Allocation of single kidney to pediatric recipient is logical and gives good long term result. However,Clinical and animal studies have demonstrated that transplanted kidneys will increase in size and function over time, provided acute rejection does not ensue. Kidneys This recipient had positive lymphocyte cross-match activity found during previous several occasions; only at this time her lymphocyte cross-match was negative. However, to protect allograft from both donor nonspecific and donor specific antibodies, we used rituximab as induction agent. Cyclosporine- or tacrolimus-based regime in recipient of pediatric kidneys fare better than historical group of azathioprime and prednisolone based regime. Nephrotoxicity of both these drugs are an issue for pediatric kidneys. Cyclosporine blunts adaptive compensatory hypertrophy; however, it occurs in lesser degree in younger kidneys.en bloc kidney transplantation from pediatric deceased donor with cyclosporine based immuno-suppression regime gives a good intermediate term graft survival. To our knowledge, this is the first case report from India to use pediatric kidneys en bloc for transplantation.Grade 1 injured kidney from deceased donor should be used for transplantation.


Sir,Traumatic testicular dislocation (TTD) is a rare complication of blunt abdominal trauma that is usually overlooked initially. Delayed A 17-year-old male motorcyclist presented with acute right groin pain after a low-velocity head-on-collision. He was hemodynamically stable, had a well-developed empty right hemiscrotum with an ovoid tender swelling in the ipsilateral groin and overlying skin ecchymosis . His lefTesticular dislocation is defined as the displacement of normally located testis to a position other than the scrotum. TTD is usually related to straddle injuries from motorcycle accidents where the rider is propelled forward, with the scrotum and perineum striking the fuel tank. The shape of fuel tank is such that it drives a smooth wedge into the groin area, forcibly displacing each testis in supero-lateral direction. In traumDislocation may be unilateral or bilateral, superficial  or internal . Possible sites with relative frequency are: superficial inguinal 50%, pubic 18%, penile 8%, canalicular 8%, truly abdominal 6%, perineal 4%, acetabular 4% and crural 2%.[Finding of an empty hemiscrotum on palpation is the key toward establishing diagnosis, though a scrotal hematoma may mask it. Differential diagnosis includes an undescended testis, retractile testis, or traumatic torsion testis with high lying testis. Doppler ultrasound scan should be performed to confirm intact viable testis and to exclude coexisting problems, i.e. testicular rupture, torsion or hematoma.Closed reduction may be attempted as the initial treatment; however, associated testicular torsion or rupture is a contraindication for closed reduction and these should be ruled out by imaging before attempting closed reduction. Successful testicular reduction means testicle in its normal anatomic intrascrotal location and immediate pain relief. Surgical exploration is preferred because of possibility of testicular torsion/rupture, high failure rate of closed reduction and minimal surgical morbidity. SurgicalThis case emphasizes upon thorough evaluation of trauma patients in emergency room including routine bilateral testicular palpation during secondary survey to avoid delayed or missed diagnosis of testicular dislocation, especially in victims of motorcycle accidents.


The metabolism of amyloid precursor protein (APP) and β-amyloid (Aβ) is widely studied in Alzheimer's disease, where Aβ deposition and plaque development are essential components of the pathogenesis. However, the physiological role of amyloid in the adult nervous system remains largely unknown. We have previously found altered cerebral amyloid metabolism in other neuroinflammatory conditions. To further elucidate this, we investigated amyloid metabolism in patients with Lyme neuroborreliosis (LNB).The first part of the study was a cross-sectional cohort study in 61 patients with acute facial palsy  and 22 healthy controls. CSF was analysed for the β-amyloid peptides Aβ38, Aβ40 and Aβ42, and the amyloid precursor protein (APP) isoforms α-sAPP and β-sAPP. CSF total-tau (T-tau), phosphorylated tau (P-tau) and neurofilament protein (NFL) were measured to monitor neural cell damage. The second part of the study was a prospective cohort-study in 26 LNB patients undergoing consecutive lumbar punctures before and after antibiotic treatment to study time-dependent dynamics of the biomarkers.In the cross-sectional study, LNB patients had lower levels of CSF α-sAPP, β-sAPP and P-tau, and higher levels of CSF NFL than healthy controls and patients with Bell's palsy. In the prospective study, LNB patients had low levels of CSF α-sAPP, β-sAPP and P-tau at baseline, which all increased towards normal at follow-up.Amyloid metabolism is altered in LNB. CSF levels of α-sAPP, β-sAPP and P-tau are decreased in acute infection and increase after treatment. In combination with earlier findings in multiple sclerosis, cerebral SLE and HIV with cerebral engagement, this points to an influence of neuroinflammation on amyloid metabolism. CSF levels of α-sAPP and β-sAPP are reduced in MS and cerebral systemic lupus erythematosus SLE [The trans-membranous protein amyloid precursor protein (APP) has been intensely studied in Alzheimer's disease (AD), since it is the source of β-amyloid (Aβ) peptides, recognized as key-components in AD pathophysiology . Althougosus SLE , and eveosus SLE .Borrelia burgdorferi. LNB is often manifested by cranial nerve engagement, and common clinical findings are facial nerve palsy and radiculitic pain [Lyme neuroborreliosis (LNB) is caused by a central nervous system (CNS) infection by the tick-borne spirochete tic pain ,6. CommoThe project contained two clinical studies. The first was a cross-sectional study in patients with acute facial palsy caused by either LNB or idiopathic Bell's palsy. The second was a longitudinal prospective cohort-study, where LNB patients were followed with successive lumbar punctures to investigate time-dependent biomarker dynamics.6/l and erythrocytes <100 × 106/L; III. One or more of the following: a) Intrathecal antibody production against B burgdorferi sp. b) Antibodies against B burgdorferi sp. in serum. c) Erythema migrans within three months; and IV. One or more of the following: a) CSF albumin >400 mg/L. b) Oligoclonal IgG and/or IgM-synthesis on CSF protein electrophoresis. c) IgG index (CSF/serum IgG ratio)/ > .70. Bell's palsy  was defined as acute, monosymptomatic, unilateral peripheral facial paresis of unknown etiology. Bell's palsy patients were included as non-infectious palsy controls.We enrolled different study participants for the cross-sectional study and the longitudinal study. Participants included LNB patients, Bell's palsy patients and controls. Diagnostic criteria for LNB were: I. Clinical symptoms consistent with neuroborreliosis and alternative explanations excluded; II Inflammatory CSF with mononuclear cell count >5 × 10In the cross-sectional part of the study we investigated 61 patients of whom 19 fulfilled criteria for LNB and 42 were classified as Bell's palsy. Twenty-two individuals for whom CSF analysis was done because of headache or vertigo, but infection and other diseases were excluded , served as controls.The longitudinal study included 26 LNB patients with radiculitic pain and sensory disturbances. In addition, 3 patients had facial palsy, 3 had paraparesis, 1 had paresis of the accessorius nerve, and 1 had a trigeminus paresis. There was no overlap with the patients in the cross-sectional study. Ten patients without any neurological disorders, undergoing knee replacements, where CSF was drawn before surgery  Abeta Triplex Assay as described by the manufacturer . This assay employs the 4G8 antibody to capture Aβ and C-terminal specific antibodies to specifically capture Aβ38, Aβ40 and Aβ42. All isoforms are detected by SULFO-TAG™-labeled anti-4G8 detection antibody. CSF concentrations of α-sAPP and β-sAPP were determined using the MSD® sAPPα/sAPPβ Multiplex Assay as described by the manufacturer. This assay employs the 6E10 antibody to capture α-sAPP and a neoepitope-specific antibody to capture β-sAPP. Both isoforms are detected by SULFO-TAG™-labeled anti-APP antibody p2-1.CSF levels of Aβ38, Aβ40 and Aβ42 were measured using the MSD® hTAU-Ag, Innogenetics, Ghent, Belgium) specifically constructed to measure all tau isoforms irrespectively of phosphorylation status (T-tau), as previously described [® PHOSPHO-TAU(181P), Innogenetics), as previously described [The axonal damage marker CSF T-tau was measured using a sandwich ELISA . The CSF/serum albumin ratio was calculated as: CSF albumin (mg/l)/serum-albumin (g/l).All statistical calculations were performed using SPSS 15.0 . As the distribution of quantitative measures was significantly skewed, statistical tests involving these variables were conducted using the non-parametric Kuskal-Wallis test for comparisons of multiple groups and the Mann-Whitney U test for pair-wise comparisons between groups. Quantitative variables are presented as median (range). The Spearman correlation coefficient was used for analyses of correlation between variable levels in different study groups. Statistical significance was determined at P < .05.The sponsors of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.In the cross-sectional study all groups were comparable in age. The only exception was that Bell's palsy patients were slightly younger than the controls  and Aβ42 , and Aβ40 correlated to Aβ42 , in all groups. These correlations were expected, since none of the subjects had any known amyloid plaque pathology, which could have entrapped Aβ40 and Aβ42 in the brain parenchyma. In the absence of plaques, these Aβ peptides are likely to diffuse at similar rates to the CSF. α-sAPP and β-sAPP correlated in all groups , indicating that the pathways producing these peptides are tightly synchronized LNB and Bell's palsy patients had similar T-tau levels in the cross-sectional study, indicating that there was no significant difference in the amount of cortical axonal damage between the groups Table . HoweverIn acute disease stage, LNB patients had elevated albumin ratio, reflecting blood-brain barrier dysfunction, which improved after treatment Table . In the We found signs of altered brain amyloid metabolism in LNB. CSF levels of the soluble APP-fragments α-sAPP and β-sAPP were decreased in the acute stage of the disease, and increased following treatment with antibiotics. Patients with Bell's palsy had no inflammatory activity in CSF and higher CSF α-sAPP and β-sAPP concentrations than LNB patients. These findings add to previous evidence of altered amyloid metabolism in primary inflammatory CNS diseases such as MS, cerebral SLE and HIV with cerebral engagement. In MS, α-sAPP and β-sAPP levels were significantly lower in patients with ongoing or recent disease exacerbation compared to patients in stable remission . In lighAlthough low α-sAPP and β-sAPP levels appear to be consistent findings in diseases with pronounced neuroinflammation, the picture becomes more complex when we turn to Aβ peptides. All subjects in the cross-sectional study in the current project had similar Aβ, but in the longitudinal study LNB patients had lower Aβ levels than controls. Note that the LNB patients differed in neurological symptoms between these two parts of the study. Other studies have found decreased Aβ42 in MS, bacterial meningitis and HIV with cerebral engagement  but not In principle, reduced levels of CSF sAPP could be caused by 1) decreased expression of APP, 2) decreased processing of APP into sAPP, 3) decreased clearance of sAPP into CSF, or 4) increased degradation of sAPP. Presently, it is not possible to draw definite conclusions on which of these mechanisms that operate in neuroinflammation. In cases where no clear reductions in CSF Aβ peptides are seen, such as facial palsy LNB, a decreased APP expression is unlikely. Likewise, altered APP processing with lower β-secretase activity would cause lower levels of both β-sAPP and Aβ peptides. Regarding the third possibility, decreased clearance of sAPP into CSF, it is known that Aβ42 under certain conditions might be trapped in interstitial drainage pathways . It is nIn the follow-up part of the present study LNB patients improved clinically after oral doxycycline, with dramatic effects on the radiculitic pain and a slower recovery of peripheral paresis. CSF analysis with decreased CSF inflammation measured as number of monocytic cells and normalization of the blood-brain barrier measured as albumin ratio support the excellent therapeutic effect. The LNB patients were younger than the controls, which might affect the statistical analysis of some parameters. However, in the study on MS referred to earlier, CSF levels of α-sAPP and β-sAPP decreased in both patients and controls during a 10 year follow-up . Thus, iRegarding markers of neural damage and tau pathology, we confirm earlier findings of increased CSF NFL in some LNB patients, which indicates acute damage to large myelinated axons . White mWe report an association of cerebral amyloid metabolism with LNB, with decreased CSF levels of soluble APP-fragments in the acute disease stage. Besides possible implications for diagnosis of LNB, these findings strengthen the case for a general involvement of amyloid in neuroinflammation and suggest that a physiological role of APP could be to participate in inflammatory pathways. We also confirm previous findings of elevated CSF NFL in LNB, suggesting damage to myelinated axons. Further research on amyloid metabolism in neuroinflammation will likely shed more light on the functions of APP in the adult human nervous system.KB has on one occasion received a consulting fee for an advisory board meeting from Innogenetics. The other authors have no conflicts of interest.NM, DB, LH, KB and HZ had the idea for this particular study and participated in the conception and design of the study. NM and DB drafted the paper. LH and DB recruited patients and analyzed the clinical effect. HA, KB, RA and HZ made important revisions to the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2377/10/51/prepub