Speed of recovery from major depressive episodes in a community sample of married men and women.

A discrete-time survival analysis of recovery from major depressive episodes for a sample of married Ss (N?=?119) identified several significant predictors of recovery including comorbidity for anxiety disorders or substance abuse, social support, age, and education. Furthermore, the analysis distinguished between different sources and types of social support, documenting that spouses' positive responses to the depression predict rapid recovery whereas the perception that friendships are conflictual predicts slow recovery. Finally, the analysis documented changes in the importance of predictor variables over the course of the episode. Specifically, spouse's negative reactions to the depression and S's education level became more important predictors of recovery as the episode became longer, and the recovery advantage experienced by younger respondents lessened over time. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Drinking trajectories following an initial lapse.

Relapse following alcohol treatment is a major problem for individuals who are alcohol dependent, yet little is known about the course of drinking after the initial lapse. In the current study, discrete-time survival analysis and latent growth mixture modeling were used to evaluate the time to first lapse and the trajectories of postlapse drinking in a sample of 563 individuals who received community alcohol treatment. Results showed a decreasing risk of lapsing over time. After the initial lapse, 3 trajectory subgroups provided a parsimonious representation of the heterogeneity in postlapse drinking frequency and quantity, with the majority of individuals reporting light, infrequent drinking. Covariate analyses incorporating demographics, distal risk factors, time to first lapse, and coping behavior as predictors of time to lapse and postlapse drinking trajectories indicated that alcohol dependence and coping behavior were the strongest predictors of lapsing and postlapse drinking behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Investigating onset, cessation, relapse, and recovery: Why you should, and how you can, use discrete-time survival analysis to examine event occurrence.

Illustrates how discrete-time survival analysis can address questions about onset, cessation, relapse, and recovery. Using data on the onset of suicide ideation and depression and relapse into cocaine use, the authors introduce key concepts underpinning the method, describe the action of the discrete-time hazard model, and discuss several types of main effects and interactions that can be included as predictors. Practical issues of data analysis and strategies for interpretation and presentation are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Use and misuse of syringes in anaesthesia

OBJECTIVE: To assess whether the cerebral gray and white matter volume deficits described in patients with anorexia nervosa (AN) are fully reversible with weight rehabilitation. DESIGN: A prospective cohort study using magnetic resonance imaging to examine the brains of female adolescents after weight recovery from AN. SETTING: An adolescent eating disorder program located in a tertiary care children's hospital. PARTICIPANTS: Of 13 patients who underwent a previous magnetic resonance imaging study at a low weight, 6 patients were weight recovered and underwent rescanning. All brain measures were corrected for the effects of intracranial volume and age, based on a regression analysis of a group of 34 healthy female control subjects. Scans from the patients with AN were also compared with scans from an age-matched subset of 16 healthy female controls. MAIN OUTCOME MEASURES: White matter volumes, gray matter volumes, and cerebrospinal fluid volumes in the weight-recovered AN group. RESULTS: Quantitative analysis showed that white matter and ventricular cerebrospinal fluid volumes changed significantly (P = .03 for both) on weight recovery from AN. The weight-recovered patients had significant gray matter volume deficits (P = .01) and elevated cerebrospinal fluid volumes (P = .005) compared with those of the age-matched controls. They no longer had significant (P = .30) white matter volume deficits. CONCLUSION: The finding of persistent gray matter volume deficits in patients who have recovered their weight after AN suggests an irreversible component to the structural brain changes associated with AN, in addition to a component that resolves on weight recovery.     

Standardized mortality in eating disorders--a quantitative summary of previously published and new evidence

Ten eating disorder (ED) populations were reviewed using the standardized mortality ratio (SMR) presenting new evidence for several studies. In eight of the ten samples, strong evidence (in one sample weak evidence and in one sample no evidence) supports an hypothesis of elevated SMR. We found strong evidence for an increase in SMR for anorexia nervosa (AN), whereas no firm conclusions could be drawn for bulimia nervosa (BN). Bias caused by loss to follow-up was quantified and found non-negligable in some samples (possible increase in SMR from 25% to 240%). We did not find a significant effect of gender or time period on SMR. Survival analysis showed a significant difference among the life-tables for males and females; female risk of death averaged 0.59% per year, whereas all male deaths occurred within the first 2 years after presentation. Weight at presentation had a highly significant effect on SMR, and lower weight at presentation was associated with higher SMR. Age at presentation exerted a significant unimodal effect on SMR; aggregate overall SMR was 3.6 for the youngest age group (< 20 years), 9.9 for those aged 20-29 years, and 5.7 for those aged > or = 30 years at presentation. Length of follow-up had a highly significant inverse effect on SMR; maximal SMR was 30 for female AN patients in the first year after presentation. A statistically significant increase in SMR was documented for at least up to 15 years after presentation. One study indicated a treatment effect on SMR. New evidence on causes of death suggests there are more deaths from suicide and other and unknown causes and fewer deaths related to ED than previously reported. Our findings have both research and clinical implications, with the most important clinical implication being the need for vigorous and well-directed treatment efforts from the initial presentation for treatment. An important research implication is that no single measure of mortality is sufficient; that is, only a combination of different statistics will maximize the available information.     

Predictors of survival for prostate carcinoma patients treated with salvage radical prostatectomy after radiation therapy

BACKGROUND: Salvage radical prostatectomy is a treatment option for patients with recurrent cancer following radiation therapy. This study was conducted to identify predictors of survival for patients treated with salvage radical prostatectomy. METHODS: The authors studied 86 prostate carcinoma patients who underwent salvage radical prostatectomy for locally persistent or recurrent prostate carcinoma at Mayo Clinic between 1967 and 1996. The mean interval from radiation therapy to biopsy-proven recurrence was 3.7 years (range, 6 months to 17 years). Patient age at surgery ranged from 51 to 78 years (median, 66 years). The mean follow-up after surgery was 5.8 years (range, 1.0-15.2 years). Cox proportional hazards models were used to identify clinical and pathologic factors associated with distant metastasis free survival and cancer specific survival. RESULTS: Actuarial distant metastasis free survival, cancer specific survival, and overall survival were 83%, 91%, and 85% at 5 years and 69%, 64%, and 54% at 10 years, respectively. In multivariate analysis, radical prostatectomy Gleason score and DNA ploidy were independent predictors of distant metastasis free survival and cancer specific survival. CONCLUSIONS: Postirradiation Gleason score and DNA ploidy were highly predictive of the clinical outcomes of patients treated by salvage radical prostatectomy after radiation therapy.     

Adult acute leukemia

Untreated acute leukemia is a uniformly fatal disease with a median survival time shorter than 3 months. Current treatment strategies provide a significant increase in survival time for most patients, some of whom may be cured. The majority of patients with acute leukemia, however, ultimately die of the disease or complications of treatment. The effective treatment of acute leukemia requires (1) differentiation of acute myeloid leukemia (AML) from acute lymphoblastic leukemia (ALL) and recognition of clinically relevant subtypes; (2) identification of patients who are more likely or less likely than average to benefit from a conventional treatment; and (3) selection of therapy that provides a reasonable likelihood of response with acceptable risk of toxic effects. The diagnosis of acute leukemia is established in most cases by a bone marrow aspirate that demonstrates at least 30% blast cells. The traditional criteria to distinguish between AML and ALL rely on morphology and cytochemical reactions. Immunologic analysis of antigen expression and analysis for numerical or structural chromosomal abnormalities of leukemia cells are routinely feasible. Karyotypic analysis is of prognostic importance and should be performed on all diagnostic specimens of bone marrow aspirate. Immunophenotypic analysis may be useful to confirm the disease classification in selected cases. The importance of the routine immunophenotypic characterization of acute leukemia, however, is controversial. The subtypes that must be recognized because of the need for specific treatment include (a) acute promyelocytic leukemia (APL), which is the M3 subtype of AML, and (b) the L3 subtype or mature B-cell ALL. Induction therapy for acute leukemia is treatment intended to achieve induction of complete remission (CR). Complete remission is defined as the absence of morphologic evidence of leukemia after recovery of the peripheral blood cell counts. Failure to achieve CR may be attributed to death during chemotherapy-induced bone marrow hypoplasia or to drug resistance manifested either as failure to achieve hypoplasia or as persistent leukemia after recovery from hypoplasia. Postremission therapy is treatment administered in CR to prevent or delay relapse of the leukemia. However, the majority of patients have disease relapse. Intensification of therapy is a treatment strategy designed to overcome resistance to chemotherapy. Recent clinical trials of intensified induction or postremission therapy suggest improved outcome. However, the toxic effects of dose intensification can be substantial, limiting any potential benefit of this approach. Identification of prognostic factors may allow one to estimate the likelihood of an outcome, to determine an optimal treatment strategy. It is well established that age at the time of diagnosis, leukemia cell karyotype, and whether the leukemia is de novo or secondary are factors that influence treatment decisions. Patients with favorable prognostic factors should probably receive conventional therapy. Patients with unfavorable prognostic factors have shown little benefit from conventional therapy. In addition, factors that indicate poor outcome with conventional therapy are also predictive of poor outcome with intensified therapy. Consequently, these patients should be considered for investigational therapeutic strategies. The bias may be to counsel them to accept the potential increased morbidity of such treatment before there is definite evidence of the possibility of improved outcome. Induction chemotherapy for younger patients with AML (less than 55 years of age) in general consists of one or more courses of cytarabine (ara-C) and an anthracycline or an anthracycline derivative. Randomized trials have failed to confirm that treatment with either etoposide or high-dose ara-C induces disease remission. Patients with secondary AML, high levels of CD34 antigen expression, or an unfavorable karyotype, however, may benefit from ind     

Effect of 6-aminonicotinamide on the pentose phosphate pathway: 31P NMR and tumor growth delay studies

6-aminonicotinamide (6AN) has been shown to enhance radiosensitivity in vitro, although previous in vivo studies failed to show an effect. 31P NMR spectra were obtained by using a one-dimensional chemical shift imaging technique on a first generation transplant of the CD8FI spontaneous mammary carcinoma tumor model. Spectra were obtained both before and 10 h after treatment with 6AN (20 mg/kg). Changes in pH, nucleoside triphosphate/inorganic phosphate, and phosphocreatine/ inorganic phosphate measured at 10 h post-6AN were not significant. A new peak was detected 10 h post-6AN, which was assigned to 6-phosphogluconate (6PG), indicating inhibition of the pentose phosphate pathway (PPP). Based on the spectral data demonstrating inhibition of the PPP at 10 h post-6AN, tumor-bearing mice were irradiated (15 Gy x 3 fractions) on Days 1, 10 or 11, and 21 10 h after administration of 6-aminonicotinamide (20 mg/kg). Tumor-bearing mice receiving 6AN alone (20 mg/kg x 3), radiation alone (15 Gy x 3), or saline were also studied. Tumor growth delay studies indicated that 6AN alone induced a small but significant tumor growth delay (4.3 +/- 0.8 days). Radiation alone induced a tumor growth delay of 34.5 +/- 2.7 days. Treatment with 6AN followed by radiation induced a tumor growth delay of 57.0 +/- 3.8 days. This was significantly greater than the TGD values for treatment with 6AN alone or radiation (P < 0.01). No complete regressions were noted after treatment with 6AN or radiation alone. Concomitant therapy with 6AN plus radiation yielded 6/28 complete regressions (21%), which was significantly greater than radiation (P < 0.05) or 6AN alone (P < 0.01) on this mammary carcinoma.     

Improvement in the prognosis of breast cancer from 1965 to 1984

PURPOSE: The prognosis of breast cancer has improved over the past three decades. It is uncertain, however, whether this improvement results from an increase in the cure rate, extension of the life span of uncured patients, or some combination. METHODS: From the Connecticut Tumor Registry, we obtained data on 25,091 patients with localized (node-negative) and regionally metastatic (node-positive) breast cancer who were diagnosed over the two decades between 1965 and 1984, with follow-up through 1993. The data for these patients were analyzed using a variety of parametric models to quantitate likelihood of cure and median survival time among uncured patients. These models incorporate the assumption that time to death from breast cancer follows a specific distribution. RESULTS: For patients with node-negative disease, parametric analysis revealed no significant difference in cured-fraction or median survival time over the two decades studied. For patients with node-positive disease, however, a significant increase in median survival time (P < .001) was found during the second decade (1970 to 1979). There was also a trend toward a higher cured-fraction over time, but this was not statistically significant. CONCLUSION: This study confirms that patients with node-positive disease had an improved prognosis over the two decades studied. Parametric analysis suggests that this improvement reflects primarily an increase in the median survival time for uncured patients, although there is a trend toward an increase in the likelihood of cure.     

Outcomes following mechanical ventilation in children undergoing bone marrow transplantation

Between 1976 and 1992, 869 patients <19 years of age underwent BMT at the University of Minnesota for a variety of malignant and non-malignant disorders. One hundred and ninety-six required mechanical ventilation (MV) at some time from the start of pre-BMT cyto reduction through the first year following BMT. Reasons for MV included respiratory compromise, upper airway management and non-pulmonary indications for respiratory support. In multivariate models, underlying diagnosis, receipt of HLA-mismatched marrow and the presence of acute graft-versus-host disease (aGVHD) were independent predictors of the need for MV. Indication for MV, underlying diagnosis, and presence of aGVHD were independent predictors of successful extubation. Overall survival at 2 years was 14% among MV patients and 52% among non-MV patients. While the need for MV during BMT reduces the overall likelihood of survival, 40% of children who required MV were successfully extubated; 35% of these extubated patients were long-term survivors. This outcome is better than that reported for adult BMT patients requiring respiratory support, who show survival of <5% at 6 months following BMT. Our data suggest extrapolation of outcome data from adult to pediatric patients is not appropriate and aggressive care of pediatric patients requiring respiratory support is not futile.     

Prodrugs for targeting hypoxic tissues: regiospecific elimination of aspirin from reduced indolequinones

We report the cases of three patients with anorexia nervosa (AN) who each recovered rapidly after experiencing a life-threatening episode with severe thrombocytopenia. All three cases were the typical restricting-type of AN, occurring in adolescence. They refused to be admitted to a hospital until their general condition had been severely deteriorated. Their lowest platelet counts were 2.9, 4.6, and 2.3 x 10(4)/mm3, respectively. Apparent hemorrhagic tendencies, such as purpura, gingival and nasal bleeding, and gastrointestinal bleeding were observed. The bone marrow examination showed apparent hypoplasia in two patients. No evidence of disseminated intravascular coagulation or autoantibody to platelets was detected. The platelet counts recovered rapidly by water and nutritional supplementation. The recovery from the AN itself was excellent in all three patients without specific psychotherapy.     

Utility of stress single-photon emission computed tomography (SPECT) perfusion imaging in predicting outcome after coronary artery bypass grafting

Previous studies have examined the predictors of outcome in medically treated patients with coronary artery disease (CAD). There is limited information on predictors of outcome after coronary artery bypass grafting (CABG). This study examined the predictors of outcome of 255 patients with CAD, at a mean time of 5 years after CABG for angina pectoris. The 255 patients underwent coronary angiography and stress single-photon emission computed tomography (SPECT) myocardial perfusion imaging after CABG. During a mean follow-up of 41 +/- 28 months after stress testing, there were 34 hard events (24 cardiac deaths and 10 nonfatal myocardial infarctions). The hemodynamics during stress testing, and age and gender were not predictors of events. The SPECT variables of multivessel perfusion abnormality, perfusion deficit size, and increased lung thallium uptake were predictors of death and total events by uni- and multivariate survival analysis. There were 14 events in 45 patients (31%) with multivessel abnormality and increased lung thallium uptake, 14 events in 101 patients (14%) with either multivessel abnormality or increased lung uptake, and 6 events in 109 patients (6%) with neither of these 2 variables (p = 0.0001). The annual mortality and total event rates were 7.5% and 9.5% with both variables, 3.4% and 4.3% with either variable, and 0.6% and 1.7% with neither of the variables (p = 0.01). Thus, stress SPECT perfusion imaging is useful to stratify patients after CABG into low, intermediate, and high risk groups for future cardiac events.     

Determinants of 30-day mortality of spontaneous intracerebral hemorrhage in Pakistan

BACKGROUND: The present study was undertaken to evaluate the determinants of acute (30-day) mortality after spontaneous intracerebral hemorrhage (ICH) in a developing country setting, and to compare these findings with those available from studies conducted in the West. METHODS: Medical records of 146 patients admitted to a major tertiary hospital in Karachi, Pakistan between 1990 and 1991 with a diagnosis of spontaneous ICH were reviewed. The level and intensity of care provided to these patients was similar to that available at modern neurosurgical centers. The salient prognostic indicators that were studied included hypertension, pulse pressure, GCS score, neurologic deficits, and CT-scan predictors including site, size, and intraventricular spread of hemorrhage. These data were used to determine independent predictors of 30-day mortality by univariate and multivariate analysis. Additionally, 30-day survival probabilities for these outcome predictors were also computed. RESULTS: The 30-day mortality after spontaneous ICH was 39.7%. Two-thirds of the patients had a history of hypertension. The important clinical predictors at the multivariate level included GCS score < or =8 and progressive increase in pulse pressure. The CT scan predictors included intraventricular spread of hemorrhage, ventricular enlargement, and size of the bleed. Location of the lesion did not appear to significantly influence mortality. Survival analysis showed a large clustering of deaths within the first 72 hours of hospitalization. CONCLUSIONS: The 30-day mortality rate and prognostic predictors for spontaneous intracerebral hemorrhage were found to be similar to those reported in the Western hemisphere. However, the correlation of incremental increase in pulse pressure with deteriorating prognosis was a new and significant finding.     

Physician retention in community and migrant health centers: who stays and for how long?

OBJECTIVES: This study used discrete-time survival analysis to estimate the tenure of primary care physicians in Community Health Centers (CHCs), to identify the changing risk of leaving Community Health Center employment as time passes, and to identify factors associated with a physician's likelihood of remaining in a Community Health Center. Because of dramatic differences in physician career trajectories, much of the focus was on differences between physicians with and without National Health Service Corps obligations. METHODS: Beginning with an administrative dataset at the Bureau of Primary Health Care that listed primary care physicians for each Community Health Center, the completeness and accuracy of the information provided were verified and an analytic database of all physicians working in those centers during a 21-month measurement window from January 1, 1990 through September 30, 1992 was constructed. The data included start and end dates, percent full-time equivalent status, and certain demographic characteristics. In addition, several data elements describing the Community Health Center were merged onto each physician record. These included urban or rural location, expenditure level, productivity, and federal grade. Through the use of discrete-time survival analysis, it was possible to include in the analytic sample all 2,654 physicians who worked during the period, even those who started working before January 1, 1990 and those who were still working on September 30, 1992. Survivor functions were estimated showing the proportion of physicians remaining after each quarter of their tenure (ie, after the fourth quarter of work, after the 12th quarter of work, etc). In addition, hazard functions were estimated showing the risk that a physician who had worked through the end of one quarter would leave during the following quarter. Finally, multivariate analysis demonstrated the relation of certain physician and center characteristics to the likelihood of the physician's leaving the center during each quarter. RESULTS: The median tenure of primary care physicians in Community Health Centers was approximately 3 years regardless of whether or not the physician had a National Health Service Corps obligation. But the career trajectories for the two groups of physicians varied dramatically. Most physicians left on or about their anniversary date, probably because it coincided with the end of their contract, but the effect was much more pronounced for National Health Service Corps physicians than for non-National Health Service Corps physicians. By the end of 5 years, approximately 36% of physicians who started without an National Health Service Corps obligation were still working compared with only approximately 17% of those with an National Health Service Corps obligation. CONCLUSIONS: The study demonstrates the value of discrete-time survival analysis in addressing questions related to the tenure of primary care physicians in Community Health Centers, making it possible to use data from physicians whose Community Health Center careers began before or ended after a give measurement window. Second, the study measured primary care physician tenure, providing center directors with a yard-stick against which to compare their own center's performance. Finally, the data provided some help in trying to explain differences in the propensity to stay or leave employment in Community Health Centers.     

Fos expression during the critical period in visual cortex: differences between normal and dark reared cats

BACKGROUND: Height of portal pressure correlates with severity of alcoholic cirrhosis. Portal pressure indices are not however used routinely as predictors of survival. AIMS: To examine the clinical value of a single portal pressure measurement in predicting outcome in cirrhotic patients who have bled. METHODS: A series of 105 cirrhotic patients who consecutively underwent hepatic venous pressure measurement were investigated. The main cause of cirrhosis was alcoholic (64.8%) and prior to admission all patients had bled from varices. RESULTS: During the follow up period (median 566 days, range 10-2555), 33 patients died, and 54 developed variceal haemorrhage. Applying Cox regression analysis, hepatic venous pressure gradient, bilirubin, prothrombin time, ascites, and previous long term endoscopic treatment were the only statistically independent predictors of survival, irrespective of cirrhotic aetiology. The predictive value of the pressure gradient was much higher if the measurement was taken within the first or the second week from the bleeding and there was no association after 15 days. A hepatic venous pressure gradient of at least 16 mm Hg appeared to identify patients with a greatly increased risk of dying. CONCLUSIONS: Indirectly measured portal pressure is an independent predictor of survival in patients with both alcoholic and non-alcoholic cirrhosis. In patients with a previous variceal bleeding episode this predictive value seems to be better if the measurement is taken within the first two weeks from the bleeding episode. A greater use of this technique is recommended for the prognostic assessment and management of patients with chronic liver disease.     

Cholecystokinin and pancreatic polypeptide release in diabetic patients with and without autonomic neuropathy

The present study was undertaken to investigate postprandial responses of cholecystokinin (CCK) and pancreatic polypeptide (PP) and their interrelationship in patients with diabetes mellitus (DM) with and without autonomic neuropathy (AN). Twenty-two patients with DM (seven with AN and 15 without AN) and 14 age-matched healthy controls were studied. AN was diagnosed according to several tests of cardiovascular autonomic function. CCK and PP plasma levels were measured by specific radioimmunoassays before and at several time points after the oral administration of a test meal. Basal CCK plasma levels in DM patients were normal, whereas basal PP plasma levels were increased (139 +/- 18 vs 72 +/- 7 pg/ml; P < 0.01). Integrated postprandial CCK response was increased in DM patients (208 +/- 27 vs 110 +/- 14 pmol/liter/2 hr; P < 0.05), mainly due to the patients with AN. Postprandial PP response was increased in DM patients without AN (37,273 +/- 5241 vs 13,418 +/- 3299 pg/ml/2 hr; P < 0.001) but not in those with AN (8887 +/- 3461 pg/ml/2 hr). Moreover, PP response was closely (P < 0.002) correlated with the degree of AN. A direct and linear correlation between postprandial CCK and PP responses was found in healthy controls (r = 0.78; P < 0.005) but not in DM patients. We conclude that the CCK response to a meal is increased in diabetic patients with AN, whereas the PP response is increased only with an intact autonomic nervous system.(ABSTRACT TRUNCATED AT 250 WORDS)     

Characteristics of non-participants and reasons for non-participation in a population survey in Kin-Hu, Kinmen

We analyzed the pattern of failure and clinicopathologic factors influencing the disease-free survival of 78 patients who died after macroscopic curative resection for pancreatic cancer. Local recurrence was a component of failure in 56 patients (71.8%) and hepatic recurrence in 48 (61.5%), both accounting for 97% of the total recurrence rate. About 95% of recurrences occurred by 24 months after operation. Median disease-free survival time was 8 months, and cumulative 1-, 3-, and 5-year actuarial disease-free survival rates were 66%, 7%, and 3%, respectively. Multivariate analysis showed that tumor grade (p = 0.04), microscopic radicality of resection (p = 0.04), lymph node status (p = 0.01), and size of the tumor (p = 0.005) were independent predictors of disease-free survival. Patterns of failure and disease-free survival were not statistically influenced by the type of surgical procedure performed. Median survival time from the detection of recurrence until death was 7 months for local recurrence versus 3 months for hepatic or local plus hepatic recurrence (p < 0.05). From our experience and the data collected from the literature, it appears that surgery alone is an inadequate treatment for cure in patients with pancreatic carcinoma. Effective adjuvant therapies are needed to improve locoregional control of pancreatic cancer after surgical resection.     

Ursodeoxycholic acid therapy for primary biliary cirrhosis. A 10-year British single-centre population-based audit of efficacy and survival

The effect of ursodeoxycholic acid treatment on survival in primary biliary cirrhosis was studied in 40 patients with symptomatic disease. Two patients developed early exacerbation of symptoms and stopped therapy in days; they are both alive 4 and 4 1/2 years later. The other 38 patients have continued on treatment for up to 10 years. Results were compared with 12 other similar cases previously seen but not given specific therapy. Kaplan-Meier analysis showed that ursodeoxycholic acid treatment was associated with better survival (p < 0.05) after the first two years of therapy. Predictors of favourable outcome included histological stage I disease. In 26 patients with primary biliary cirrhosis stage II, III or IV, therapy showed a trend to improved survival, but this was still significantly worse than the general population. Prognosis was not different between these different advanced stages. Symptoms improved in 28 out of 40 patients on ursodeoxycholic acid, but 50% had a recurrence by two years.     

A case of a foreign body--surgical linen left in the abdominal cavity 25 years earlier

To confirm the biological effects of peptide growth factors on auditory neuron (AN) in vitro, the influence of NFG and bFGF on the survival status and the neurite regrowth of dissociated primary AN in postnatal chicks was studied with serum-free culture technique and cytologic quantitative method. The results demonstrated that the growth of non-neuron elements such as Schwann's cell was predominant in the earlier stage of culture. The neurite regrowth (bipolarity or unipolarity) of AN was observed at 24 hours after seeding. The growth rate increase during 48-72 hours in the surviving AN. These findings indicated that both growth factors exerted direct neuronotrophic effect on dissociated AN in vitro. NGF and bFGF acted in cooperation to promote the axon regeneration of AN. The concentration-dependent effect of NGF on neurite regrowth and neurone survival was found in the present study. The biological mechanism of NGF and bFGF on AN in vitro has been discussed.     

Human high molecular weight-melanoma associated antigen mimicry by mouse anti-idiotypic monoclonal antibody MK2-23: modulation of the immunogenicity in patients with malignant melanoma

The mouse anti-idiotypic (anti-id) mAb MK2-23 bears the mirror image of the antigenic determinant defined by antihuman high molecular weight-melanoma associated antigen (HMW-MAA) mAb 763.74. The purpose of this study was to evaluate the effect of conjugation to a carrier and administration with an adjuvant and cyclophosphamide (CTX) on the immunogenicity of anti-id mAb MK2-23 in patients with malignant melanoma and to analyze the relationship between development of humoral immunity and survival time of patients. Fifty-eight patients were sequentially entered into four immunization protocols which included administration of mAb MK2-23, mAb MK2-23 conjugated to keyhole limpet hemocyanin (KLH) and mixed with Bacillus Calmette-Guérin (BCG), mAb MK2-23 and CTX, and mAb MK2-23 conjugated to KLH and mixed with BCG and CTX. Six patients could not be evaluated since they withdrew from the clinical trial after the first immunization. Sera were tested for the development of anti-anti-id antibodies, including those reacting with HMW-MAA. Testing of sera for development of antimouse Ig antibodies was used to monitor the immune competence of patients. Conjugation to KLH and administration with BCG markedly enhanced the ability of mAb MK2-23 to induce anti-anti-id antibodies, including those reacting with HMW-MAA. In contrast, pretreatment with CTX had no detectable effect on the ability of mAb MK2-23 to elicit a humoral anti-anti-id response. Kaplan-Meier survival analysis showed that the performance status of patients, anti-anti-id antibody level, and development of anti-HMW-MAA antibodies had an effect on survival time. This effect was found when the survival time was calculated both from the day of the first immunization and from 4 weeks after the first immunization to the end of the study. A multivariate analysis by Cox regression showed that the development of anti-HMW-MAA antibodies was the most important variable for predicting survival, and that performance status was the only variable that significantly added to the prediction of survival. These data have to be interpreted with caution because of the retrospective nature of the analysis. Nevertheless, the present study suggests that mAb MK2-23 represents a useful immunogen to implement active, specific immunotherapy in patients with malignant melanoma.