Normal Risk Group Research Articles

Clinical course of high and low immunological risk renal transplant receptors subjected to different immunosuppressive treatments

We evaluate the incidence of acute rejection, opportunistic infections and non-dermatological malignancies, graft and recipient survival between a group of high immunological risk renal transplant recipients and a group of patients without immunological risk, who received grafts from the same cadaveric donors since 2001 to 2006. This is a prospective and observational study. The risk group (n= 50) included patients with high rate of antibodies (> 50%), recipients who had lost their first graft due to early rejection, cross match positive, black race or important histoincompatibility. They received thymoglobulin to maintain T-cell around 10 cells/ microl, FK 506 after five days, mycophenolate mofetyl and steroids, with ganciclovir prophylaxis for CMV. The normal risk group (n=50) ,cyclosporine, mycophenolate mofetil and steroids. Recipients who lost their graft due to technical failure were excluded..All CMV seronegative recipients who received seropositive grafts were treated with valganciclovir for 100 days.The mean follow-up was 42,7 months. Both groups were similar respect to donor and recipient gender and age, HLA incompatibility, but the percentage of patients with high rate of performed antibodies and second transplant recipients was higher in the high risk group according to the criteria of the study The incidence of acute rejection histologically diagnosed was higher in the normal risk group (30% against 6 %, p=0.03). There was no difference in opportunistic infections or malignancies, although 2 recipients of the normal risk group developed lymphoproliferative disorders. The recipients survival was 97,9% at 1 and 3 years in both groups, and the graft survival was 89,8% and 84,8% in the high risk group against 93,8 % and 90,4% at 1 and 3 years in the normal group (p=NS). We conclude that the evolution of high risk renal transplant recipients is similar to normal risk patients if a potent enough immunosuppression is used. The incidence of acute rejection was higher in the normal risk group.

Acute and long-term outcome of unprotected left main coronary angioplasty compared to the anticipated surgical risk

Percutaneous coronary intervention of unprotected left main (ULM) stenosis is increasing despite surgical revascularisation being the recommended treatment by the current guidelines. We compared the 30-day and 9-month mortality after ULM stenting with the predicted surgical outcome as determined by the EuroSCORE. We included 81 consecutive patients who underwent ULM stenting. The patient cohort was divided into a normal risk group (EuroSCORE <or=5, predicted 30-day mortality <3%), and a high-risk group (EuroSCORE >5, predicted 30-day mortality 11%). Follow-up examinations were scheduled for one and nine months after the initial PCI. The average EuroSCOREs in the normal- and high-risk group were 3.0 (29 patients, 36%) and 10.0 (52 patients, 64%), respectively. Mortality rates at 30 days were 3% in the normal-risk group and 8% in the high-risk group. Subacute stent thrombosis occurred in 3.4% (three patients) undergoing elective PCI. Major adverse cardiac events during the nine months follow-up were registered in 24% of patients in the normal-risk group, and in 27% of the patients in the high-risk group. Short-term outcome of ULM stenting in our high-risk patients is comparable to surgical outcome predicted by the EuroSCORE. Long-term outcome was less favourable due to a high mortality rate. ULM stenting in patients with low surgical risk could be associated with higher mortality rates compared to CABG because of the unpredictable risk of a fatal stent thrombosis.

Psychosocial and Physical Impairment in Overweight Adolescents at High Risk for Eating Disorders

Many overweight adolescents display elevated risk for the development of eating disorders, as seen in higher rates of weight/shape concerns and disordered eating behaviors, but the extent of impairment in this subset of high-risk adolescents has not been explored. Eighty-one overweight adolescents (63% girls) presenting for an Internet-based weight loss program were assessed at baseline using the Eating Disorder Examination Questionnaire, the Depression, Anxiety, and Stress Scale, and the Pediatric Quality of Life questionnaire. Adolescents who earned elevated scores on both the Weight Concern and Shape Concern subscales of the Eating Disorder Examination Questionnaire were considered at high risk for the development of eating disorders (56.8%). Comparisons of high- and normal-risk groups revealed that high-risk adolescents reported higher levels of depression [F(3,76) = 5.75, p = 0.019], anxiety [F(3,76) = 5.67, p = 0.020], and stress [F(3,75) = 8.50, p = 0.005], and greater impairments in physical health [F(3,77) = 10.7, p = 0.002], emotional functioning [F(3,77) = 5.3, p = 0.024], and social functioning [F(3,77) = 10.0, p = 0.002]. There were no differences in school functioning [F(3,77) = 1.5, p = 0.219]. Among the high-risk adolescents, over half (52.2%) reported binge eating at least once in the past month. Results suggest that overweight adolescents at high risk for the development of eating disorders also experience elevated levels of negative affect, impairment in health-related quality of life, and eating disturbances, although prospective data are needed to determine the directionality between eating disorder pathology and general psychopathology. Further research is warranted to evaluate whether behavioral weight loss interventions should be enhanced for this high-risk subset.

PCR-Based MRD Detection in AML with Normal Karyotype or Other intermediate Risk Aberrations by the Use of FLT3-LM, NPM1-Mutations, MLL-PTD or WT1-Overexpression.

The prognostic value of MRD detection in AML has been shown for PML-RARA, AML1-ETO, and CBFB-MYH11positive AML, a group which accounts for only 20–25% of AML. The largest group of AML is represented by cases with normal karyotype or unbalanced intermediate risk group karyotypes. In this group different molecular mutations occur, which are associated with heterogeneous clinical outcome. Thus, different MRD patterns can be anticipated. To expand the spectrum of molecular targets in intermediate risk AML, we used MLL-PTD, FLT3-LM, and NPM1 which are detectable in 45–50% of all intermediate risk group pts for MRD detection. In addition, overexpression of WT1 for MRD detection was used to even include pts. without detectable mutations. In total 996 samples (spl) of 234 patients (pts) were analysed by quantitative real time PCR. For MLL-PTD (321 spl of 78 pt), and WT1 (336 spl of 66 pts) universal assays were used. For NPM1 mutation specific assays (182 spl of 54 pts (42 x type A, 2 x type B, 7 x type D, 3 x rare not yet defined types)) and for FLT3-LM (161 spl of 18 selected pts) patient specific assays were used. All assays were RNA based. Sensitivity of the assays were between 1:100.000 to 1:1.000.000 for the FLT3-LM and NPM1, depending on pts specific assay. Sensitivity was 1:10.000 to 1:100.000 for MLL-PTD due to low background levels detectable in healthy controls. The sensitivity of WT1 was relatively low with 1:100 at most, as there was no high WT1 expressor at diagnosis in this cohort. With all markers the clinical course of the disease was clearly be reflected and all 84 relapses were detectable due to recurring high expression rates. In 17 cases, were samples 2–4 months before clinical relapse were available relapses were predictable based on increasing transcript levels. Five different follow up intervals (int) were defined: up to day 21; days 22–60; days 61–120; day 121–365, later. The log change from diagnosis to defined follow up intervals was analyzed. A rapid decline of median transcript ratios in the NPM1 group (int 1: 2 log; int 2 to 4: 4 log) was observed. Relapses in the NPM1 group occurred earliest after one year. AML with FLT3-LM similarly showed good responses with 1–2 log decreases in int 1 and 2 and 3 log in int 3 and 4. Also this group revealed the first relapses in int 5. The MLL-PTD group was characterized by slow response rates with only 0.2 log reduction in int 1 and 2 and hardly 3 log in int 3. In this group many relapses occurred in int 4 and 5. These data reflect the biological differences of these molecular subgroups: NPM1 as a favourable group, FLT3-LM as a slightly unfavourable group with good response rates but high relapse rates, and MLL-PTD as an entity with bad prognosis due to poor response rates and high relapse rates. Due to low sensitivity WT1 reflected only 0.2 log in interval 1 up to 2 log in interval 3. Seven cases were analyzed in parallel for WT1 and MLL-PTD, 6 for WT1 and FLT3-LM, and one for FLT3-LM and MLL-PTD. Although the correlation of parallel assessment was high (R=0.993) the median differences of log changes of FLT3-LM and NPM1 was one log larger than for MLL-PTD and three log larger than for WT1, depending on the initial sensitivity of the assays. In conclusion: MRD detection is feasible in the karyotypically intermediate risk group. it nicely reflects biological difference in this group NPM1, MLL-PTD and FLT3-LM are better MRD-markers than WT1, which may only be investigated in cases without any other available marker.

Age-dependent morphological alterations of human ovaries from populations with and without BRCA mutations

Objective. From analysis of pre-cancer ovarian tissues obtained from prophylactic oophorectomies, several studies reported the increased ovarian morphological changes in high-risk ovaries, but whether these morphological changes are associated with BRCA1/BRCA2 genotypes or are cancer precursors is controversial. Here, we have investigated a recent collection of ovaries from prophylactic oophorectomies and control ovaries from surgeries due to other non-ovarian-related cancer or non-neoplastic diseases to determine if ovarian morphological changes relate to BRCA1/2 genotypes or reproductive history. Methods. We assembled a panel of archived ovarian tissues: 52 ovarian tissue blocks were from prophylactic oophorectomies of a high-risk (HR) population; 66 ovaries were from surgeries due to non-ovarian-related diseases, referred to as normal-risk (NR) group. The morphology of ovarian tissues was examined, and morphological changes including papillomatosis, invaginations, inclusion cysts, and epithelial stratification were assessed in a blinded fashion. Results. No statistically significant difference in frequency of these histolopathologic features was found between HR and NR groups. However, inclusion cysts and deep invaginations were found much more commonly in women age 45–54 of either HR or NR groups. Conclusions. This study suggests that no significant increase in the presence of non-neoplastic ovarian morphological changes is associated with BRCA1/BRCA2 mutations. Rather, the frequency of these histological features, especially inclusion cysts, may associate with age or menopausal status. We propose that ovulatory and perimenopausal gonadotropin stimulation produces ovarian morphological changes, and these histological features may promote the transformation of genetically compromised epithelial cells in the development of ovarian cancer.

Adult Acute Lymphoblastic Leukemia and Cytogenetic Abnormalities in Different Racial and Ethnic Subgroups.

Inferior survival of African American and Hispanic patients with acute lymphoblastic leukemia (ALL) has been reported. The reason for this is unclear. A retrospective analysis was conducted to see if abnormal cytogenetics account for the differences. We have analyzed cytogenetic studies of 39 adults (16 year and older) with newly diagnosed ALL who were consecutively treated at John Stroger Hospital of Cook County between 1997 and 2005. The study population included 13 (33%) African Americans, 18 (46%) Hispanics, 6 (16%) Caucasians, and 2 (5 %) other ethnic background adults. Male to female ratio was 2:1. Mean age at diagnosis was 26 (range between 16 and 71 years). A clonal cytogenetic abnormality was detected in 27 patients, and 12 patients had normal karyotype. Patients with t (9;22)(q34;q11), BCR-ABL + by FISH, t (4;11)(q21;q23), +8, −7 cytogenetic abnormalities were assigned to an unfavorable cytogenetic group. This group was composed of 14 patients. None of our study patients had favorable cytogenetics: del (12p), t(12p), t(14q11-q23), inv(14)(q11;q32) or t(10;14)(q24;q11). Remaining 25 patients with normal karyotype (n=12) or miscellaneous cytogenetic abnormalities (n=13) were classified as normal risk group. 54 % of African Americans had unfavorable cytogenetics, compared with 33 % Caucasians and 17 % Hispanics. Translocation t (9;22) alone or in association with other cytogenetic abnormalities was most commonly seen. 9 patients had single, and 18 had multiple chromosomal changes. Hispanic group had more complex cytogenetic changes when compared with the African American or Caucasian groups. Unfavorable cytogenetic abnormalities may account for inferior survival in African Americans, but other factors such as compliance or pharmacogenetics should be evaluated, especially in the Hispanic patient population.

Does Heart Transplantation Confer Survival Benefit in All Risk Groups?

Over 50,000 heart transplants have been performed in the last 3 decades. The global shortage of donor organs and the relaxation of candidate selection criteria over time has resulted in recent controversy about the benefits of heart transplantation for some risk groups. We assessed the survival benefit acquired in the Papworth Hospital heart transplant population overall, taking into account resuscitated marginal donors and high-risk recipients. All heart transplant patients listed between 1979 and June 2002 were analyzed (n = 1,212). Of these, 931 cardiac transplantations were done, including the use of 126 marginal donors. High-risk recipients (n = 163) were defined as patients being in the hospital, on intravenous inotropic drugs, and/or with a high transpulmonary gradient (>15 mm Hg). Using Cox regression with transplantation as a time-dependent covariate, we assessed the survival benefit of transplantation. In our model we assumed that after transplantation the initial risk of death is high relative to continued waiting, followed by an exponential decline in risk. The crossover point (COP) is the time at which the risk of death after transplantation is equal to that of continued waiting (i.e., the relative risk is 1). The equity point (EP) determines the time at which the early post-operative risk is offset by the later period of lower risk and, therefore, the time at which transplantation has a survival advantage. Overall, the COP was at 54 days and EP at 141 days. In the marginal donor sub-group, COP was achieved at 32 days with EP at 72 days, indicating a survival benefit. The difference in the COP and EP between the borderline donor and normal donor sub-groups was not statistically significant. Post-transplant survival was not significantly different from recipients of normal cardiac allografts (p = .43). Likewise, for the high-risk recipient group, the COP and EP were at 72 and 203 days. Although post-op survival was significantly shorter than the normal-risk group, both groups achieved survival benefits. Heart transplantation provides survival benefit in these risk groups of recipients in our population. This is a reflection of our active donor management protocol and rigorous donor and recipient selection process.

Single pretransplant bolus of recombinant activated factor VII ameliorates influence of risk factors for blood loss during orthotopic liver transplantation

Large blood loss and transfusions during liver transplantation (LTx) may lead to serious complications and have a negative impact on post-transplant mortality and morbidity. In the retrospective study we compared two groups of recipients of primary cadaveric liver transplantation: group I (study group), consisted of 28 patients with preoperative risk of high intraoperative blood loss, including severe uncorrected coagulopathy. This group was given a bolus of recombinant activated factor VII (rFVIIa) just before LTx. Group II (control group) included 61 patients without a particular risk for increased intraoperative blood loss. These patients were not given rFVIIa. We analyzed both groups for: coagulation parameters before, during and after surgery (INR, APTT, factor VII activity), blood and FFP transfusions, operative time, postoperative complications (vascular thrombosis, reoperation for bleeding), postoperative ICU stay, post-transplant hospitalization time and mortality. Patients from the study group (I) had significantly worse coagulation parameters than patients in the control group (II) at the start of the surgical procedure; however, after administration of a bolus of rFVIIa there was immediate correction of coagulation in all recipients. No significant differences in intraoperative blood transfusions were observed between study and control groups (1980 +/- 311.4 mL vs. 1527 +/- 154.2 mL, respectively), operating time (8.7 h vs. 8.9 h) or ICU and hospital stay (7.03 days vs. 6.15 days and 40.89 days vs. 41.1 days). Re-exploration because of bleeding was performed in three patients from group I (10.7%) and in seven patients (11.5%) from group II. No single case of vascular thrombosis was observed in the study group, while in the control group there were three hepatic artery thromboses, two portal vein thromboses and one hepatic vein thrombosis. We conclude that rFVIIa given preoperatively to liver transplant recipients with several risk factors for high intraoperative bleeding adjusts these patients to a normal risk group, without an increased risk for thrombotic complications.

The utility of the international child and adolescent overweight guidelines for predicting coronary heart disease risk factors

The purpose of this study was to assess the association between the international overweight cutoffs for children and youth and coronary heart disease risk factors. The sample included 410 boys and 337 girls 9–18 years of age from the Québec Family Study. Participants were classified as normal weight or overweight using the international BMI cutoffs, and into normal and elevated risk groups based on the 90th percentile of sex-specific age-adjusted risk factors [blood pressure, fasting total cholesterol (CHOL), LDL-C, HDL-C, CHOL/HDL-C, triglycerides, glucose, and physical work capacity]. Overweight participants had between 1.6 and 9.1 times the risk of elevated risk factors compared to normal-weight participants. Further, boys and girls with four or more risk factors were 19 and 43 times more likely to be overweight, respectively, compared to participants with no risk factors. The results add evidence that the international cutoffs are related to health risks in youth, supporting the adoption of the guidelines.

Interleukin-6 and risk of coronary artery disease and graft failure in heart transplant recipients

The difference in the COP and EP between the borderline donor subgroup and all others was not statistically significant. Post-transplant survival was not significantly different from recipients of normal cardiac allograft (p 0.43). Likewise for the high-risk recipient group, the COP and EP were at 72 and 203 days respectively. Although post-op survival was shorter than the normal risk group, both groups achieve a survival benefit. Conclusion: Heart transplantation has survival benefit in both these risk groups of recipients and donors in our population reflecting our rigorous donor and recipient selection and management.

High-risk carotid endarterectomy: fact or fiction.

It has been proposed that patients whose conditions do not meet North American Symptomatic Carotid Endarterectomy Trial inclusion criteria or have anatomic risk factors constitute a "high-risk" group for carotid endarterectomy (CEA) and might be candidates for primary carotid angioplasty stenting. Our objective was to review a consecutive series of isolated CEAs, identify the number of such patients at high risk, and determine whether their operations were associated with increased complication rate. Consecutive isolated CEAs performed between June 1996 and June 2001 were reviewed. High-risk comorbidities included: age 80 years or more (n = 80), New York Heart Association class III/IV angina (n = 16), Canadian class III/IV heart failure (n = 4), myocardial infarct 6 months or less (n = 11), steroid-dependent or oxygen-dependent pulmonary disease (n = 4), and creatinine level of 3 or more (n = 13). Anatomic high risk was defined by: contralateral occlusion (n = 66), lesion above C(2) or requirement of digastric division (n = 53), reoperation (n = 29), and neck radiation (n = 3). Statistical analysis was with chi(2) analysis. Of 788 patients reviewed, 228 (29%) were classified as high risk by one or more of the previous criteria (63% comorbidity, 28% anatomy, 9% both). Presence of preoperative neurologic symptoms and postoperative results were similar across all patient groups. The total stroke and death rate was 1.1% for all the patients. Six patients had postoperative strokes (0.8%), and three patients died of myocardial infarcts (0.4%). The stroke and death rate was 1.3% in the high-risk group as compared with 1.1% in the normal-risk group (P =.51). The concept of the high-risk CEA must be critically reexamined. Although 29% of patients for CEA were high risk as defined by others, we found no evidence that this influenced the results after CEA. Patients with significant medical comorbidities, contralateral carotid occlusion, and high carotid lesions can undergo operation without increased complications. If a high-risk group exists, it is small and restricted to reoperation or radiated neck (4% in this series). With this possible exception, carotid angioplasty stenting should be restricted to randomized clinical trials.

Neuromotor markers of risk for schizophrenia.

To evaluate the possibility of using neuromotor deviation (NMD) as an individual-orientated, early life marker for increased risk for schizophrenia. Previous findings based on systematic examination of NMD are summarised concerning schizophrenia patients and individuals at heightened genetic risk for schizophrenia. Significantly increased rates of NMD are found in patients with schizophrenia, both after and long before disease onset. Neuromotor deviation can be efficiently studied at all ages from infancy to adulthood, and is typically not in itself stigmatising. Neuromotor deviation may represent an unstable characteristic of individuals from infancy to middle-to-late childhood, possibly attaining greater stability thereafter. Neuromotor deviation may also be more stable over time in the high-risk offspring of parents with schizophrenia than in other children. Neuromotor deviation in childhood predicts subsequent serious mental disturbance in genetic high-risk children. The efficiency of NMD for predicting schizophrenia in unselected samples is unknown, as is the optimal age(s) for assessing NMD to predict schizophrenia in high-risk and normal-risk groups. Neuromotor deviation is also found in the well relatives of schizophrenia patients, individuals developing a broad range of mental and physical disorders, and mentally normal individuals in the general population. Neuromotor deviation should definitely be included in batteries of methods for identifying individuals with notably heightened risk of schizophrenia. However, NMD is not pathognomonic for schizophrenia, and the investigation of NMD during childhood and adolescence must thus be used judiciously in order to avoid possible stigmatisation. Further research should be done concerning the specific forms and developmental timing of NMD as related to schizophrenia.

Childhood leukaemia in areas with different radon levels: a spatial and temporal analysis using GIS

OBJECTIVESTo evaluate the relation between exposure to ground radon levels and leukaemia among children using existing population and disease registers.DESIGNEcological correlation study.SETTINGThe county of Östergötland in Sweden.METHODSEvery child born in...

Neuromotor Markers of Risk for Schizophrenia

Objective To evaluate the possibility of using neuromotor deviation (NMD) as an individual-orientated, early life marker for increased risk for schizophrenia. Method Previous findings based on systematic examination of NMD are summarised concerning schizophrenia patients and individuals at heightened genetic risk for schizophrenia. Results Significantly increased rates of NMD are found in patients with schizophrenia, both after and long before disease onset. Neuromotor deviation can be efficiently studied at all ages from infancy to adulthood, and is typically not in itself stigmatising. Neuromotor deviation may represent an unstable characteristic of individuals from infancy to middle-to-late childhood, possibly attaining greater stability thereafter. Neuromotor deviation may also be more stable over time in the high-risk offspring of parents with schizophrenia than in other children. Neuromotor deviation in childhood predicts subsequent serious mental disturbance in genetic high-risk children. The efficiency of NMD for predicting schizophrenia in unselected samples is unknown, as is the optimal age(s) for assessing NMD to predict schizophrenia in high-risk and normal-risk groups. Neuromotor deviation is also found in the well relatives of schizophrenia patients, individuals developing a broad range of mental and physical disorders, and mentally normal individuals in the general population. Conclusions Neuromotor deviation should definitely be included in batteries of methods for identifying individuals with notably heightened risk of schizophrenia. However, NMD is not pathognomonic for schizophrenia, and the investigation of NMD during childhood and adolescence must thus be used judiciously in order to avoid possible stigmatisation. Further research should be done concerning the specific forms and developmental timing of NMD as related to schizophrenia.

HIV-Related Non-Hodgkin's Lymphoma: CHOP Induction Therapy and Interferon-α-2b/Zidovudine Maintenance Therapy

In a prospective multicenter study 68 out of 158 patients with HIV infection and malignant lymphoma were assigned to a risk-adapted induction therapy using the following algorithm: High-risk patients fulfilled 2 of 3 criteria: T4 lymphocytes < 50/μ:L; WHO activity index 3 or 4; pre-existing AIDS-defining opportunistic infection. Normal-risk patients received 4 to 6 cycles of CHOP chemotherapy; those that achieved complete remission (CR) received zidovudine (500 mg/d) and interferon-α maintenance therapy (5 million units three times a week) for one year. High-risk patients received low-dose CHOP or vincristine/prednisone chemotherapy. Supportive care was performed with pentamidine inhalation and G-CSF. Intrathecal (it) methotrexate was given for CNS prophylaxis.The median survival was 634 days for 38 patients of the normal-risk group and 129 days for 30 patients of the high-risk group. 18 high-risk patients treated with low-dose CHOP had better survival (156 days) than 12 patients treated with vincristine/prednisone (72 days p = 0.044). 68% of the patients in the normal-risk group achieved complete remission. 5 out of 18 high-risk patients treated with low-dose CHOP achieved complete remission. Three normal-risk patients developed fatal opportunistic infections during chemotherapy. Immune parameters deteriorated after CHOP induction and partially recovered with maintenance treatment.We conclude that the normal-risk patients survived longer than reported in most published studies. Toxicity was low. Low-dose CHOP seems to be superior to vincristine/prednisone therapy in high-risk patients.

Postoperative complications of penetrating keratoplasty in herpes infected eyes. Differential diagnosis, therapy and prognostic significance

We evaluated in this retrospective study the impact of our diagnostic and therapeutic regimens--as illustrated by typical clinical pictures--on the frequency and prognostic values of postkeratoplasty complications in herpes eyes. Between November 1986 and June 1994, 112 penetrating keratoplasties (KPS) in herpes eyes were performed, 76 as planned and 36 as emergency procedures. The results were compared with 646 KPS with normal risk. For statistical analysis we used the Kaplan-Meier estimation, and statistical significance was tested by the log rank test. After 6 years, 75% of the grafts in the planned herpes group, 86% of the à chaud KPS and 76% of the grafts of the normal-risk group were still clear without significant differences between these three groups. Fifty-four percent of the planned KPS in herpes eyes, 73% of the à chaud KPS in herpes eyes and 80% of the normal-risk KPS experienced no immune reaction, with both herpes groups showing significantly more reactions than the normal-risk KPS. There was, however, no significant difference in immune reactions between the two herpes groups. The percentage of grafts with recurrence of herpes simplex virus infection after 6 years was significantly higher in the à chaud group. With proper postoperative care and optimal management of immunologic and virologic complications--but only with this!--the prognosis of penetrating keratoplasties in herpes eyes equals that of normal risk eyes. An particular, the prognosis is not dependent on whether surgery was performed as a planned or as an emergency procedure.

Epidemiology, outcome and control of varicella-zoster infection

Summary Chickenpox is a mild disease in children, but may be life threatening in immunosuppressed patients, neonates and normal adults, particularly smokers in whom the risk of varicella pneumonia is high. Infection during the first 5 months of pregnancy carries a small risk (probably <1%) of congenital varicella syndrome characterised by unilateral limb hypoplasia, dermatomal skin scarring and neurological damage. However, the greatest burden of morbidity attributed to varicella-zoster infection arises from herpes zoster, which affects 1 in 4 adults by the eighth decade of life. The epidemiology of chickenpox appears to be changing with an unexplained upward shift in the age distribution of cases over the last 20 years. This has important consequences for future mortality rates, and the risk of infection in pregnancy and health care workers. The effectiveness of existing prophylactic and therapeutic measures for varicella zoster infection are reviewed and the potential uses of varicella vaccine are discussed in the light of current evidence of its safety and efficacy in normal and high risk groups.

Minor congenital malformations and mental characteristics during childhood: high-risk and normal-risk groups.

Among children with normal psychiatric risk, those born with (even minor) congenital malformations (CMs) evidenced significantly poorer attention persistence in early childhood, as well as greater anxiety-proneness, poorer interpersonal relational competency, and more mental disturbance at six years of age. No significant relationship between CMs and mental characteristics was found in children at heightened psychiatric risk.

The use of oncofetal ferritin-bearing lymphocytes as a marker for the screening, diagnosis, and follow-up of patients with early breast malignancy screening of 3400 women.

The potential of using a blood test enumerating oncofetal ferritin-bearing lymphocytes (FBL) as a biomarker for early breast cancer was further explored. Nine hundred women attending a high-risk breast cancer clinic and 2500 normal-risk women were physically examined and their blood drawn for FBL determination using a newly developed radioimmunoassay. The FBL test results were compared to clinically or histopathologically diagnosed breast disease and to known breast cancer risk factors. A gradual increase in the mean FBL ratio was seen from normal risk disease-free women to those with in situ or early stage breast cancer. The percentage of women with positive FBL was 13.6% for the normal risk group, 19% and 25.7% for clinically and histopathologically diagnosed benign breast disease, respectively, and 100, 77.8, and 66.7% for in situ, Stage I, and Stage II breast cancer, respectively. In locally advanced disease (Stage III) the percentage of positive women was only 17.2%. It was further found that a negative FBL result in known breast cancer patients at Stage I, II of the disease was a bad prognostic marker indicating a shorter disease-free survival. The follow-up of patients after surgery by periodical clinical examination and the FBL test revealed that the positive FBL was declining after removal of the precancerous or malignant tumor and that it was highly sensitive (100%) in predicting tumor development and recurrence. Using a logistic regression analysis, an FBL-positive test indicated a significant association with risk of early breast cancer (odds ratio = 2.9; 95% confidence interval = 1.4-5.8). Being a measure of the immune response the positive FBL was associated with early breast cancer and good prognosis. Since patients with locally advanced cancer and poor prognosis were FBL negative but such patients were shown to have increased serum ferritin levels. It is suggested to use the FBL and serum ferritin assays for screening and diagnosis of breast cancer.

Effective technique of sternum closure in high-risk patients.

A successful technique of closing the sternum in a selected group of poor-risk patients involves the combination of a mattress suture and a fixative single-wire suture, both of 0 stainless-steel monofilament. Our technique was used on 100 high-risk patients and compared with double control groups, one consisting of 200 normal-risk patients and the second of 100 high-risk patients. We found that the incidence of wound infections was reduced to 1% with our new technique compared with 3% and 1% in the control groups (the high- and normal-risk groups, respectively). There was neither dehiscence nor mediastinitis in the study group, compared with 1% and 0.5% incidences of these complications in the controls. Also, there was no mortality in the combined-closure group compared with mortality of 0.5% and 1% in the control groups. We believe that this closure effectively strengthens the complex of bone and wire, improving the stability of the chest by giving a correct axis to the sternum. It is also cost-effective and easy to perform and does not prolong operation time.