Postpartum Depression-Identifying Risk and Access to Intervention.

PURPOSE OF REVIEW: As maternal mortality climbs in the USA with mental health conditions driving these preventable deaths, the field of reproductive psychiatry must shift towards identification of women and other birthing individuals at risk and facilitating access. This review brings together recent studies regarding risk of perinatal depression and highlights important comorbidities that place individuals at higher vulnerability to poor perinatal outcomes. RECENT FINDINGS: Recent research suggests that identifying risk for perinatal depression including historical diagnoses of depression, anxiety, trauma, and comorbid substance use and intimate partner violence may move the field to focus on preventive care in peripartum populations. Emerging data shows stark health inequities in racial and ethnic minority populations historically marginalized by the health system and in other vulnerable groups such as LGBTQ+ individuals and those with severe mental illness. Innovative models of care using systems-level approaches can provide opportunities for identification and risk analyses of vulnerable peripartum patients and facilitate access to therapeutic or preventive interventions. Utilizing intergenerational approaches and leveraging multidisciplinary teams that thoughtfully target high-risk women and other birthing individuals could promote significant changes to population-level care in maternal health.

Thiothymidine combined with UVA as a potential novel therapy for bladder cancer.

BACKGROUND: Thiothymidine (S(4)TdR) can be incorporated into DNA and sensitise cells to DNA damage and cell death following exposure to UVA light. Studies were performed to determine if the combination of S(4)TdR and UVA could be an effective treatment for bladder cancer. METHODS: Uptake and incorporation of S(4)TdR was determined in rat and human bladder tumour cell lines. Measures of DNA crosslinking and apoptosis were also performed. In vivo activity of the combination of S(4)TdR and UVA was investigated in an orthotopic model of bladder cancer in rats. RESULTS: Thiothymidine (200 µM) replaced up to 0.63% of thymidine in rat and tumour bladder cancer cells. The combination of S(4)TdR (10-200 µM) and UVA (1-5 kJ m(-2)) caused apoptosis and cell death at doses that were not toxic alone. Addition of raltitrexed (Astra Zeneca, Alderley Edge, Cheshire, UK) increased the incorporation of S(4)TdR into DNA (up to 20-fold at IC(5)) and further sensitised cells to UVA. Cytotoxic effect was associated with crosslinking of DNA, at least partially to protein. Intravenous administration of S(4)TdR, in combination with UVA delivered directly to the bladder, resulted in an antitumour effect in three of five animals treated. CONCLUSION: These data indicate that the combination of S(4)TdR and UVA has potential as a treatment for bladder cancer, and give some insight into the mechanism of action. Further work is necessary to optimise the delivery of the two components.

The role of folate receptor alpha (FRalpha) in the response of malignant pleural mesothelioma to pemetrexed-containing chemotherapy.

BACKGROUND: The standard treatment of choice for malignant pleural mesothelioma is chemotherapy with pemetrexed and platinum, but the clinical outcome is poor. This study investigates the response to pemetrexed in a panel of eight mesothelioma cell lines and the clinical outcome for patients treated with pemetrexed in relation to folate receptor alpha (FRalpha). METHODS: Cell lines were treated with pemetrexed to determine the concentration that reduced growth to 50% (GI(50)). FRalpha expression was determined by western blotting and that of FRalpha, reduced folate carrier (RFC) and proton-coupled folate transporter (PCFT) by real-time quantitative RT-PCR. Immunohistochemistry for FRalpha was carried out on 62 paraffin-embedded samples of mesothelioma from patients who were subsequently treated with pemetrexed. RESULTS: A wide range of GI(50) values was obtained for the cell lines, H2452 cells being the most sensitive (GI(50) 22 nM) and RS5 cells having a GI(50) value greater than 10 microM. No FRalpha protein was detected in any cell line, and there was no relationship between sensitivity and expression of folate transporters. FRalpha was detected in 39% of tumour samples, generally in a small percentage of cells. There was no correlation between the presence of FRalpha and the outcome of pemetrexed treatment, and no significant difference between histological subtypes. CONCLUSION: Response to treatment with pemetrexed does not depend on the presence of FRalpha.

Changes in expression of oncogenes and endogenous retroviral-like sequences during colon carcinogenesis.

The possible roles in experimental colon carcinogenesis of two protooncogenes (c-myc and c-H-ras), two endogenous retrovirus-related DNA sequences [rat leukemia virus (RaLV) and the 30S sequence], and two cell cycle related genes (beta-actin and ornithine decarboxylase) were studied by analyzing the levels of their corresponding RNAs during the course of azoxymethane induced and high fat promoted colon carcinogenesis. F-344 male rats received three s.c. injections of azoxymethane (15 mg/kg) or normal saline and were then subdivided into high or low fat diet groups. During subsequent serial sacrifices normal colon mucosa, adenomas, and carcinomas were harvested for histology and RNA extraction. Seventy-one RNA samples were analyzed by the Northern blot hybridization procedure using the appropriate 32P-labeled DNA probes. A marked increase in the abundance of c-myc, RaLV, and 30S RNAs were seen in all of the colon tumors, including adenomas and invasive carcinomas. No or a very low level of expression of RaLV and c-myc RNA was found in the flat grossly normal mucosa adjacent to the tumors and in the mucosa of the control rats. Some of the colon tumors also displayed increased levels of c-H-ras, ornithine decarboxylase and beta-actin RNAs but these findings were less striking and more variable than those seen with c-myc, RaLV, and 30S RNAs. These results suggest that increased expression of the c-myc protooncogene and of the endogenous retrovirus-like sequences (RaLV) and 30S are hallmarks of colon carcinogenesis in this model system.

Distribution of the c-myc oncoprotein in normal and neoplastic tissues of the rat colon.

A rat model of 5-azoxymethane induced colon cancer was studied in order to correlate histopathological changes and the differential distribution of the c-myc protein. Weanling Fisher 344 rats were injected with three, one week apart, subcutaneous injections of 5-azoxymethane (AOM) (15 mg kg-1) and the animals were divided into low and high fat diet groups. Nine colon tumors, of varying degrees of malignancy, that developed in the AOM-treated rats, and sections of normal colonic mucosa were examined. A rabbit polyclonal anti-c-myc antibody produced nuclear staining at 1:100 dilution in cryostat frozen sections of the normal rat colonic mucosa and the colon tumors when prepared with a Cryostat Frozen Sectioning Aid (CFSA). The tissue localization of the c-myc antibody staining revealed: (1) in normal mucosa, nuclei of the basal portion of the mucosa; (2) in adenomatous polyps, nuclei at all levels of the mucosa; and (3) in a carcinoma in situ, intense staining of glandular epithelial cell nuclei at all levels within the tumor. This procedure may provide a sensitive method for detecting abnormal cells in the colonic epithelium that have an altered proliferative capacity.

Increasing incidence and excellent survival of patients with early gastric cancer: experience in a United States medical center.

PURPOSE: In Japan, early gastric cancer has an excellent survival rate. In the United States, the disease is less well understood, and it is viewed more pessimistically, although we have previously shown in a small series of patients good short-term survival rates in early gastric cancer as compared with advanced gastric cancer. Our purpose in this study was to determine if the incidence of early gastric cancer and the associated survival rate has changed over a 24-year period. PATIENTS AND METHODS: From the records at the Columbia Presbyterian Medical Center, 549 patients were identified who underwent gastric resection for cancer between 1960 and 1984, 69 of whom had early gastric cancer. Survival data were obtained in 63 patients. A comparison of survival rates was conducted between patients with early gastric cancer and the 1980 census figures. RESULTS: Over the 24-year period, the total number of resections for gastric cancer at our institution declined. However, the percentage of gastric resections that satisfied the Japanese criteria for early gastric cancer increased from 9 percent between 1960 to 1974 to 17 percent between 1975 to 1984 (p less than 0.05). Of the 69 early gastric cancers, 35 percent involved the mucosa, whereas in 65 percent the malignancy invaded the submucosa. Twenty-eight percent had lymph node involvement. For the patients for whom survival data were available, survival was better than the 1980 census (p less than 0.05). The adjusted five-year survival rate was 97 percent. Neither submucosal invasion nor lymph node involvement altered survival. Patients with type III early cancers (ulcerated), however, had a significantly greater survival rate than patients with type I (polypoid) early cancers (p less than 0.05). CONCLUSION: Early gastric cancer is being diagnosed with increasing frequency and has an excellent survival rate. These findings are similar to the Japanese experience and argue for an ongoing aggressive approach to endoscopic biopsy of gastric lesions.

Changes in biochemical disease-free survival rates as a result of adoption of the consensus conference definition in patients with clinically localized prostate cancer treated with external-beam radiotherapy.

PURPOSE: The optimal definition of biochemical recurrence of prostate cancer after definitive radiotherapy remains elusive. Different institutions have developed their own definitions, and a consensus conference (CC) sponsored by the American Society for Therapeutic Radiology and Oncology has recently proposed another definition. This study compares the definition previously used at our institution with the definition proposed by the CC. METHODS: Two hundred and eight patients were treated for localized prostate cancer with conformal external-beam radiotherapy between 1989-1993 at our institution and followed for at least 24 months. Patients were categorized as failures according to our institutional definition and the CC definition. Our definition (CPMC) required two increases in serum prostate specific antigen (PSA) over at least a 3-month period with a final value of at least 1 ng/ml or a single value resulting in clinical intervention. The CC definition required three consecutive increases in PSA. This was modified to also consider those patients with one or two increases leading to clinical intervention as failures. Differences in the failure rates between the two definitions were evaluated and factors influencing these differences were explored. In an additional analysis, CC was modified such that patients with one or two PSA increases were censored at the time of the PSA prior to the increases (CC-II), rather than at the last PSA (CC). The median follow-up time was 31 months. RESULTS: There were 36 fewer failures according to CC (n = 96) compared with CPMC (n = 132) (p < 0.001). Twenty cases called failures by CPMC subsequently had a decrease in PSA ("false failures"). The other 16 patients have had two increases in PSA, but are awaiting their next follow-up visit to obtain a third PSA ("pending failures"). Analysis of factors predicting "pending failures" showed Gleason score to be the sole predictor of this change in status in multivariate analysis (p = 0.03) with patients with lower-grade tumors being more likely to change status (Gleason 2-6: 15% vs. Gleason 7-10: 1%). On the other hand, "false failures," compared to true failures, had a lower mean PSA nadir (1.7 ng/ml vs. 7.0 ng/ml, p < 0.001) and significantly smaller mean increases in PSA (1st increase: 0.6 ng/ml vs. 3.4 ng/ml, p = 0.006; 2nd increase: 0.4 ng/ml vs. 4.8 ng/ml, p = 0.002). In 85% (17 of 20) of these patients, at least one of the increases was < or = 0.3 ng/ml compared with 44% (42 of 96) of the true failures (p = 0.0008). CC-II resulted in a small decrease in BDFS rates compared with CC, but did not affect the overall difference between CC and CPMC. A modified definition that defines failure as two consecutive increases in PSA over 3 months, with a final value greater than 1.0 ng/ml and each increase being at least 0.3 ng/ml, or three consecutive increases would result in a "false" failure rate of only 3% (3 of 99) and identify 56% (54 of 96) of the true failures after only two PSA increases. CONCLUSION: The CPMC definition of two PSA increases can falsely identify patients as failures, particularly if the increases in PSA are small (i.e., < or = 0.3 ng/ml). The CC definition requiring three increases in PSA can falsely identify patients as disease-free when the time to failure is long relative to the follow-up time. We propose a that a definition that combines aspects of both definitions (two consecutive increases in PSA over 3 months, with a final value greater than 1.0 ng/ml and each increase being at least 0.3 ng/ml, or three consecutive increases) may be a better definition of biochemical failure.

Should a Gleason score be assigned to a minute focus of carcinoma on prostate biopsy?

The grading system for prostate carcinoma devised by Gleason is a strong prognostic indicator. The primary and secondary patterns are combined to give a tumor score, referred to as Gleason score or sum. Gleason scores on biopsy correlate with the prostatectomy Gleason scores, and in combination with pretreatment serum prostate-specific antigen and digital rectal examination results, predict tumor stage and lymph node status. However, when only a minute focus of tumor is present on biopsy, the Gleason score is assigned by doubling the Gleason pattern. The goal of this study was to determine if a Gleason score assigned to a minimal focus of adenocarcinoma had predictive value. Paired biopsies and prostatectomy specimens from 963 cases of men with clinically localized prostate cancer were examined. Minimal tumor on biopsy was defined as less than 1 mm or 5% involvement of one biopsy core; excluded from this definition were biopsies where two Gleason patterns could be identified and/or tumor was seen on more than one biopsy core. Terms often used to describe these lesions include "single minute focus of carcinoma" or "adenocarcinoma, too small to give a Gleason grade." One hundred five cases (10.9%) met the above criteria for minimal carcinoma. The correlation of Gleason scores between biopsies and prostatectomy specimens overall was good with exact agreement for 57% of cases and a difference of +/-1 unit in 92% of cases. The correlation for the minimal tumors on biopsy and prostatectomy was slightly worse with exact agreement in 52.4% (55 of 105) and a difference of +/-1 unit in 87.6% (92 of 105). The majority of minimal tumors (83.8% or 88 of 105) were assigned a Gleason score of 6. A total of 31.8% of these 88 cases were upgraded and 5.7% were downgraded. Multivariate analysis on all cases looking for predictors of tumor stage found biopsy Gleason score, perineural invasion, pretreatment prostatic-specific antigen, and digital rectal examination all predicted higher tumor stage with odds ratios of 1.86 (95% confidence interval [CI], 1.53-2.27; p = 0.0001), 2.06 (95% CI, 1.43-2.95; p = 0.0001), 1.08 (95% CI, 1.05-1.11; p = 0.0001), and 1.41 (95% CI, 1.04-1.91; p = 0.0289), respectively. In a model restricted to the 105 cases with minimal carcinoma, pretreatment prostatic-specific antigen was the only independent predictor of higher tumor stage with an odds ratio of 1.15 (95% CI, 1.01-1.31; p = 0.0380); Gleason score was not found to significantly predict higher tumor stage (odds ratio, 1.156; p = 0.6680). The results of this study confirm that biopsy Gleason score in most cases predicts prostatectomy Gleason score and tumor stage. However, for cases with minimal tumor on biopsy, the assigned Gleason score did not predict tumor stage. To properly convey this uncertainty to clinicians, a cautionary note should accompany Gleason scores derived from a minimal focus of carcinoma.

Cribriform carcinoma of the prostate and cribriform prostatic intraepithelial neoplasia: incidence and clinical implications.

Cribriform neoplasia of the prostate can be recognized easily. However, controversy persists regarding terminology, particularly with the intraductal spread of cribriform neoplasia; some consider this "intraductal carcinoma," whereas consensus meetings defined these lesions as high-grade cribriform prostatic intraepithelial neoplasia (HGCP). This study attempts to identify the incidence and clinical significance of HGCP and cribriform carcinoma (CC) by evaluating 114 radical prostatectomy specimens. Cases were divided into three histologic groups for statistical analysis: (1) pure acinar carcinoma: infiltrating acinar carcinoma without evidence of cribriform neoplasia; (2) CC: acinar carcinoma with CC; and (3) HGCP: acinar carcinoma with HGCP. High-grade cribriform prostatic intraepithelial neoplasia was defined as the presence of neoplastic cells spanning the entire lumen in a cribriform configuration in which a basal cell layer could be shown by immunohistochemistry. Similar areas in which no basal cell layer could be seen were diagnosed as CC. The incidence of cribriform neoplasia was 38% (43 of 114). The incidences of HGCP and CC were 13% (15 of 114) and 25% (28 of 114), respectively. Univariate analysis showed a strong association between HGCP and CC both and several preoperative and final pathology results, including digital rectal examination, pathology tumor stage, extraprostatic extension, surgical margin positivity, high Gleason sum (GS), and high tumor volume. Kaplan-Meier analysis showed HGCP to have a 61% cumulative prostate-specific antigen (PSA) failure rate in contrast with CC and pure acinar cancer, which had cumulative PSA failure rates of 15% and 13%, respectively (p = 0.0001, log-rank test). Multivariate Cox's proportional-hazards analysis found preoperative serum PSA, GS, tumor stage, and volume to be important predictors of PSA failure. In a second regression model that included serum PSA, GS, and pathology tumor stage, HGCP was an independent predictor of PSA failure. Both HGCP and CC are closely associated with several poor prognostic indicators, including advanced pathology tumor stage, a high GS, and serum PSA. Multivariate analysis showed HGCP as an independent prognostic indicator. The close association between high tumor volume and HGCP supports the theory that the development of HGCP is a late event in tumor progression, more compatible with the intraductal spread of tumor than dysplasia.

Endocrine changes associated with the human aging process: III. Effect of age on the number of calcitonin immunoreactive cells in the thyroid gland.

The thyroid glands obtained at autopsy from 60 patients ranging in age from 16 to 89 years were immunostained for calcitonin (CT) by the peroxidase-antiperoxidase procedure. The numbers of CT immunoreactive cells identified were 0.99 +/- 1.07/mm2 in the young patients (16 to 39 years of age), 0.99 +/- 1.46/mm2 in the middle-aged (40 to 59 years of age), and 2.97 +/- 3.69/mm2 in the elderly (60 years of age and older). The results were not statistically significant because of the large standard deviation. The CT immunoreactive cells tended to aggregate in clusters in a pattern similar to that seen in C-cell nodules in older persons.

The effect of age on the number of pituitary cells immunoreactive to growth hormone and prolactin.

The results of a combined immunocytochemical, morphometric, and clinicopathologic analysis of growth-hormone-producing and prolactin-producing pituitary cells in 28 subjects ranging in age from 16 to 90 are reported. There was a significant age-related decline in the number and size of growth-hormone-producing cells, which was most marked in the transition from youth to middle age. There was also a significant age-related decline in the number of pituitary parenchymal cells but not in pituitary weight. Prolactin cells did not show a significant decline in number with age.

Endocrine changes associated with the human aging process: II. Effect of age on the number and size of thyrotropin immunoreactive cells in the human pituitary.

The thyrotropin immunoreactive cells in the pituitaries of 40 patients of varying ages were quantified after immunocytochemical staining. Thyrotroph hypertrophy and relative hyperplasia were both present in aged pituitaries. No consistent relation with the histologic features of the thyroid or adrenal, or with the cause of death, was demonstrable.

Cystic duct occlusion and transcatheter sclerosis of the gallbladder in the rabbit.

We have identified a reliable sclerosant of the gallbladder in rabbits. After ligating the cystic ducts with a silk ligature in 24 rabbits and aspirating the bile from the gallbladder, we instilled a mixture of 95% ethanol and either 2 M% trifluoroacetic acid (TFA) or 5 M% TFA into the gallbladder. The animals were killed after 6 or 8 weeks. Ethanol with TFA resulted in replacement of gallbladder lumen with fibrous tissue in 22 rabbits. The two sclerosants were equally reliable and produced quantitatively similar fibrosis in the rabbits. The tendency for normal biliary mucosa to repopulate a sclerosed gallbladder can be obviated by complete occlusion of the cystic duct. The parameters for successful transcatheter sclerosis of the gallbladder have now been defined in an animal model.

Transcatheter sclerosis of the gallbladder in rabbits. A preliminary study.

Catheter sclerosis of 56 rabbit gallbladders was attempted at laparotomy. The proximal cystic duct was occluded with a hemoclip and transcatheter administration of six different sclerosing agents and a saline control was performed. Eight animals were used for each agent, three being sacrificed after two weeks and the remainder after six weeks. Hot contrast and sotradecol were comparable with saline in their lack of effect on gallbladder mucosa. Alcohol alone, tetracycline, methylcyanoacrylate and alcohol plus trifluoroacetic acid were successful at two weeks in denuding the gallbladder epithelium and promoting fibrosis of the gallbladder wall. After six weeks, evidence of mucosal regeneration was present with all agents, and the epithelium appeared to have grown back from the occluded cystic duct. Late regeneration has not been previously reported and its significance when considering the application of the technique to the human gallbladder is discussed.

Phase I study of busulfan, cyclophosphamide, and timed sequential escalating doses of cytarabine followed by bone marrow transplantation.

In both animal models and human studies in leukemia, residual disease on day 8 following myelosuppressive therapy is in a proliferative phase and therefore may be sensitive to the S-phase specific drug cytarabine. Based on this concept, 17 patients with refractory or relapsed leukemia or lymphoma undergoing either autologous or allogeneic bone marrow transplantation (BMT) were treated on a Phase I protocol using high doses of busulfan (16 mg/kg, days -10, -9, -8, -7) and cyclophosphamide (120 mg/kg, days -6, -5) followed by escalating doses of a 48-h continuous infusion of cytarabine (starting dose 1000 mg/m2/48 h, days -3, -2). Ten patients received autologous transplants (two with Hodgkin's disease, seven with non-Hodgkin's lymphoma, one with chronic myelogenous leukemia (CML) in blast phase). Seven received allogeneic BMT (two with refractory acute myelocytic leukemia (AML), one with refractory acute lymphoblastic leukemia (ALL) undergoing a second BMT, one with Burkitt's-type leukemia, one with ALL in fifth relapse and two with CML in accelerated/blast phase). Two of these patients received a T cell-depleted haploidentical transplant. The maximum tolerated dose of cytarabine was 1500 mg/m2/48 h; a pulmonary syndrome including dyspnea, hypoxemia, and interstitial infiltrates which responded to aggressive diuresis was the dose limiting toxicity. Of the 10 patients who received cytarabine doses of 2000 or 2500 mg/m2/48 h, five patients developed adult respiratory distress syndrome (ARDS) with three patients requiring intubation; two recovered. Of the nine patients with lymphoma, seven responded with complete tumor clearance (CTC) with two patients tumor-free 13 and 15 months post-BMT, one remained refractory and one died too early to evaluate (TETE).(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchiolitis obliterans organizing pneumonia as a complication of allogeneic bone marrow transplantation.

We report a patient who underwent two allogeneic bone marrow transplants for chronic myelogenous leukemia, initially in 1984 and again after relapse in 1990, who developed an identical pulmonary syndrome at a similar interval following each transplant. The patient presented with a non-productive cough, bilateral inspiratory crackles, and multiple patchy infiltrates on chest X-ray. Pulmonary function testing revealed a restrictive abnormality but no obstructive defects. The appearance of this pulmonary disorder after each transplant coincided with the development of chronic graft-versus-host disease. In both instances, this pulmonary syndrome completely reversed with corticosteroid therapy. The patient's chest computed tomographic scan and lung biopsy specimens were consistent with the diagnosis of bronchiolitis obliterans with organizing pneumonia (BOOP). While bronchiolitis obliterans has been reported following allogeneic transplant, BOOP has not previously been reported in this setting.

Thrombotic thrombocytopenic purpura associated with FK506 following bone marrow transplantation.

Thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) have been observed after bone marrow transplantation (BMT), typically occurring 1-6 months following BMT. We describe two patients who developed TTP very early after BMT while receiving intravenous FK506. They were treated with platelet support and plasma exchange (PE) using either fresh frozen plasma (FFP) or cryosupernatant fraction of plasma (CFP), resulting in remission of TTP activity.

Allogeneic bone marrow transplantation with matched unrelated donors for patients with hematologic malignancies using a preparative regimen of high-dose cyclophosphamide and fractionated total body irradiation.

Allogeneic bone marrow transplantation (BMT) from an HLA-identical sibling donor is effective therapy for patients with bone marrow failure states and those with hematologic malignancies. However, only a minority of them will have an HLA-identical sibling donor; unrelated donors, matched or partially mismatched, have been used successfully for patients lacking a related donor. Even though results with allogeneic transplants using unrelated donors are encouraging, the incidence of complications including graft-versus-host disease (GVHD) and graft rejection or late graft failure is increased compared to identical sibling transplants. The combination of cyclophosphamide and total body irradiation (TBI) has been used as an effective preparative regimen for allogeneic transplants, however, the total dosage and dosing schedule of both the cyclophosphamide and TBI has varied significantly among studies. To decrease the rate of graft rejection and late graft failure with volunteer donors, we evaluated a preparative regimen of high-dose cyclophosphamide (200 mg/kg over 4 consecutive days, days -8, -7, -6, -5) followed by fractionated TBI (1400 cGy administered in eight fractions over 4 days, days -4, -3, -2, -1). GVHD prophylaxis included FK506 and methotrexate. From July 1993 to January 1996, 43 adult patients, median age 38 years (range 18-58 years), were treated with this preparative regimen. Seventeen patients had low-risk disease and 26 had high-risk disease. Thirty-one donor/recipient pairs were matched for HLA-A, -B, and -DR by serology and molecular typing. Seven additional pairs were minor mismatched at the HLA-A or HLA-B loci. Four other donor/recipient pairs were HLA-A,-B, and -DR identical by serology but allele mismatched at either DRB1 or DQB. Forty patients were evaluable for myeloid engraftment. Engraftment occurred in all 40 patients at a median of 19 days. There were no cases of graft rejection or late graft failure. Nephrotoxicity was the primary adverse event with 26 patients (60%) experiencing a doubling of their creatinine. Hepatic veno-occlusive disease occurred in seven patients, six of whom had high-risk disease. All patients who had relapsed or refractory disease prior to BMT achieved a complete remission following BMT. Six patients transplanted for high-risk disease relapsed a median of 377 days post-BMT. None of the patients with low-risk disease have relapsed following transplant; the Kaplan-Meier survival for those patients with low-risk disease is 62% and 37% for those patients transplanted with high-risk disease (P = 0.0129). The median Karnofsky performance status is 100% (range 70-100%). Therefore, a preparative regimen of high-dose cyclophosphamide and fractionated TBI is an acceptable regimen for patients receiving an allograft from unrelated donors.

The use of the implantable chemoinfusion pump in the treatment of hepatic metastases of colorectal cancer.

Fifty-five chemoinfusion devices have been implanted in patients with metastasis of colorectal cancer confined to the liver. There were no episodes of pump malfunction or of catheter clotting. Side effects included gastric ulcers in 13 patients and duodenal ulcers in four patients, including one episode of total gastric obstruction. Chemical hepatitis occurred in 13 patients, sclerosing cholangiolitis in one patient, and duodenal dismotility requiring gastroenterostomy in one patient. The response criterion was taken as reduction by at least 50% of the pretreatment carcinoembryonic antigen level; consequently, the response rate was 88%. Median survival of all patients was 19.2 months from the time of diagnosis of hepatic metastases to death, as determined by the Kaplan-Meier method. Median survival from the time of pump implantation to death was 10.1 months.

Effects of methylphenidate on attention and nonverbal learning in children with attention-deficit hyperactivity disorder.

OBJECTIVE: To examine effects of methylphenidate (MPH) doses on attention and learning tasks requiring varying levels of processing in 23 children with attention-deficit hyperactivity disorder. METHOD: Performance on a continuous performance task (CPT) and two difficulty levels of a nonverbal learning task was evaluated on two doses of MPH (0.3 mg/kg and 0.8 mg/kg) and placebo. RESULTS: CPT commission errors were significantly reduced with low-dose MPH compared with placebo while omission errors were not medication-sensitive. Performance on nonverbal learning tasks was significantly improved with MPH. On the easy level of the nonverbal learning task performance improved equally well with either dose. On the hard level, performance was significantly better at the high dose compared with placebo; no between-dose differences emerged across learning trials. However, the high dose was superior to low and placebo doses in memory recall trials. CONCLUSIONS: Impulsivity may be reduced on an attentional task with a low dose of MPH, and a high dose of MPH may optimize retention and recall of complex nonverbal information.