Comparative outcomes among the problem areas of interpersonal psychotherapy for depression.

BACKGROUND: Although interpersonal psychotherapy (IPT) is an efficacious treatment for acute depression, the relative efficacy of treatment in each of the four IPT problem areas (grief, role transitions, role disputes, interpersonal deficits) has received little attention. We evaluated the specificity of IPT by comparing treatment success among patients whose psychotherapy focused on each problem area. Moreover, we sought to understand how the patient characteristics and interpersonal problems most closely linked to the onset of a patient's current depression contributed to IPT success. METHODS: Patients meeting DSM-IV criteria for an episode of major depressive disorder (n=182) were treated with weekly IPT. Remission was defined as an average Hamilton Rating Scale for Depression 17-item score of 7 or below over 3 weeks. Personality disorders were diagnosed using the Structured Clinical Interview for DSM-IV Personality Disorders. RESULTS: Contrary to our prediction that patients whose treatment was focused on interpersonal deficits would take longer to remit, survival analyses indicated that patients receiving treatment focused on each of the four problem areas did not differ in their times to remission. Nor were patients in the interpersonal deficits group more likely to have an Axis II diagnosis. Patients whose treatment focused on role transitions remitted faster than those whose treatment focused on role disputes, after controlling for covariates. CONCLUSION: With skillful use of IPT strategies and tactics and with careful medication management where appropriate, patients in this study whose treatment focused on each problem area were treated with equal success by trained IPT clinicians.

Association of childhood and adolescent anthropometric factors, physical activity, and diet with adult mammographic breast density.

Early-life exposures may influence the development of breast cancer. The authors examined the association of childhood and adolescent anthropometric factors, physical activity levels, and diet with adult mammographic breast density, a strong risk factor for breast cancer. Women in the Minnesota Breast Cancer Family Study cohort who had undergone mammograms but had not had breast cancer (n=1,893) formed the sample. Information on adolescent exposures, including relative height, weight, and physical activity at ages 7, 12, and 18 years and diet at age 12-13 years, was self-reported during two follow-up studies (1990-2003). Mammographic percent density was estimated using a computer-assisted thresholding program. Statistical analyses were performed using linear mixed-effects models with two-sided tests. Positive associations with height at ages 7 (p<0.001), 12 (p<0.001), and 18 (p<0.001) years and percent density were evident overall and within menopausal status categories. The minimum difference in percent density between the tallest and shortest girls was 3 percent, with a maximum of 7 percent. Weight at age 12 years (p=0.005) and adiposity at age 12 years (p=0.005) were both inversely associated with adult percent density. Adolescent physical activity and diet were unrelated to percent density. These results suggest that adolescent height, a known risk factor for breast cancer, is also associated with mammographic percent density.

Microscopic correlation of radiographically disparate appearing well differentiated osteosarcoma.

Well differentiated (low grade) osteosarcomas are often unrecognized and inadequately treated. We report on a patient with a well differentiated osteosarcoma of the tibia that radiographically presented with two strikingly dissimilar appearing juxtaposed lesions. Proximally, the lesion was sclerotic, and distally, osteolytic. The distal lytic half of the lesion showed focal cortical disruption on MR imaging. Microscopic correlation of the resected specimen suggested that the sclerotic component of the lesion had more fibrous dysplasia-like tissue with fewer features of well differentiated osteosarcoma, and the lytic component, features suggestive of well differentiated osteosarcoma. We believe this microscopic interpretation explains the disparate radiographic appearance as all belonging to well differentiated osteosarcoma with varying amounts of fibrous dysplasia-like tissue rather than the development of well differentiated osteosarcoma in fibrous dysplasia.

Acral synovial chondrosarcoma.

Acral chondrosarcoma is rare. Synovial chondrosarcoma is even rarer. Synovial chondrosarcoma arising without evidence of pre-existing or concurrent synovial chondromatosis is exceedingly rare. We present a case of acral synovial chondrosarcoma involving both sides of the metacarpophalangeal joint of the thumb in a 69-year-old man. Radiographically, the lesion mimicked gout. On MR imaging, the lobulated contours of the soft tissue mass suggested synovial chondromatosis. Histological examination revealed a chondrosarcoma, which on the basis of imaging findings we present as having arisen from the synovium. The tumor invaded a portion of the cartilage of the metacarpophalangeal joint and equally destroyed the bones of the distal metacarpal and base of the proximal phalanx of the thumb, while sparing the bony joint surfaces.

Periosteal chondroid tumors: radiologic evaluation with pathologic correlation.

OBJECTIVE: The purpose of this study was to determine whether the imaging features of periosteal chondroid tumors correlate with histopathology. MATERIALS AND METHODS: Twenty-two patients (nine women and 13 men; mean age, 33 years) with pathologically proven periosteal chondroid lesions were retrospectively reviewed. The imaging modalities included conventional radiography (n = 17), CT (n = 10), and MR imaging (n = 14). The images were reviewed by two osteoradiologists, with agreement by consensus. Evaluation criteria included lesion location, mineralization, and size; periosteal reaction; and cortical response. Intramedullary extension, adjacent intramedullary edema, soft-tissue edema, and intrinsic characteristics were also evaluated on MR imaging. After the evaluation, a radiologic diagnosis of chondroma or chondrosarcoma was obtained. An experienced osteopathologist who was unaware of the patient's medical history and radiologic findings reviewed all histopathology. Agreement between the radiologic and the histopathologic diagnosis was tested using the kappa analysis. Imaging features were correlated with the pathologic findings, and a statistical analysis was performed. RESULTS: Using strict pathologic criteria, we diagnosed 11 chondromas and 11 chondrosarcomas (nine, grade I; two, grade II). Moderate agreement was reached between the radiologic and the pathologic diagnosis (kappa = 0.55). The size of periosteal chondrosarcomas (range, 3-14 cm; median, 4 cm) was considerably larger than the size of the chondromas (range, 1-6.5 cm; median, 2.5 cm; p < 0.05). Other imaging features did not significantly correlate with benign versus malignant disease at pathology (all p > 0.05). CONCLUSION: A variable overlap existed in the imaging appearances of benign and malignant periosteal chondroid lesions, with size being the most reliable indicator in distinguishing the two lesions. This and the fact that histologic differentiation of the entities can be difficult, suggests that surgical wide excision may be the most appropriate procedure in treating patients with lesions greater than 3 cm.

Histological evaluation of iron in liver biopsies: relationship to HFE mutations.

OBJECTIVE: Hepatic iron overload is observed in many forms of chronic liver disease. Hereditary hemochromatosis (HH) results in hepatic iron overload and is associated with 2 missense mutations in the HFE gene. The aim of this study was to define the usefulness of the histological pattern of iron deposition in determining the probability of an iron-loaded patient having HFE-related iron overload. METHODS: This study assessed liver biopsies containing stainable iron from 103 patients with various liver diseases; clinical information included hepatic iron concentration and HFE genotype (C282Y, H63D). The biopsies were evaluated using a reproducible histological scoring system for iron deposition. Three separate components of histological iron deposition were recorded: 1) pattern (primarily hepatocellular with a zonal gradient, or reticuloendothelial without an obvious zonal gradient), 2) pattern score to denote the extent of iron within the acinus, and 3) quantitation grade of iron granules within affected hepatocytes. RESULTS: The predominantly hepatocellular pattern (HH pattern) was observed in 72 biopsies of which only 42 were from patients homozygous for the C282Y mutation, indicating that this pattern alone cannot be used as a surrogate marker for HH genotype. The predominantly reticuloendothelial pattern (non-HH pattern) was observed in the remaining 31 patients, none of whom was compound heterozygous or homozygous for the C282Y mutation (negative predictive value: 100%). Thus, the non-HH, reticuloendothelial pattern reliably predicts the absence of homozygosity for the C282Y mutation. CONCLUSIONS: The use of histological evaluation for iron deposition is simple, assists in expanding information communicated from histopathologic observations, and may be clinically useful in determining the necessity of further evaluation of HFE genotype in subjects with histological evidence of hepatic iron overload.

Repetitive self-limited acute pancreatitis induces pancreatic fibrogenesis in the mouse.

The role of repetitive acute injury in the pathogenesis of chronic pancreatitis remains unknown. To determine if repetitive injury induced by pancreatic hyperstimulation would reproduce the characteristic features of human chronic pancreatitis, acute reversible pancreatic injury was induced in mice by twice weekly cerulein treatment, 50 microg/kg/hr x 6 hr, for 10 weeks. Procollagen alpha1(I) mRNA was markedly increased by week 2. Sirius red staining of interstitial collagen demonstrated progressive accumulation of extracellular matrix surrounding acinar units and in interlobular spaces. Atrophy, transdifferentiation of acinar units to ductlike tubular complexes, and dilatation of intraacinar lumina also developed. Electron microscopy demonstrated the presence of stromal cells in areas of fibrosis with morphologic characteristics of pancreatic stellate cells. These findings demonstrate that, in a murine model, repetitive acute injury to the pancreas by hyperstimulation can reproduce the major morphological characteristics of human chronic pancreatitis.

Myxoma of the humerus: an exceptional site of origin.

Myxoma of bone, outside of the jaws, is exceptional. We present such a tumor in the humerus and discuss the criteria for the diagnosis of myxoma.

Gabapentin in bipolar disorder: a placebo-controlled trial of adjunctive therapy. Gabapentin Bipolar Disorder Study Group.

OBJECTIVES: [corrected] To assess efficacy and safety of gabapentin in the treatment of bipolar disorder. METHODS: This was a double-blind, placebo-controlled trial of adjunctive gabapentin (dosed flexibly between 900 and 3,600 mg/day). Patients with a lifetime diagnosis of bipolar disorder (type I), and who were currently suffering from symptoms of either mania, hypomania or a mixed state despite ongoing therapy with lithium, valproate, or lithium and valproate in combination were eligible for inclusion. The primary efficacy measures were the baseline to endpoint change in total score on the Young Mania Rating Scale (YMRS) and the Hamilton Depression Rating Scale (HAM-D). RESULTS: Both treatment groups had a decrease in total YMRS from baseline to endpoint, but this decrease was significantly greater in the placebo group (-9) than the gabapentin group (-6) (p < 0.05). No difference between treatments was found for the total score on the HAM-D. Secondary efficacy measures were not different between treatment groups. More patients in the placebo group had changes made to their ongoing lithium therapy (n = 12) compared to the gabapentin group (n = 4). When these patients are removed from the efficacy analysis, the YMRS treatment difference still favors placebo, but is no longer statistically significant. Based on gabapentin plasma levels at termination, some patients did not take the study drug as prescribed. CONCLUSIONS: The findings of this study did not demonstrate that gabapentin is an effective adjunctive treatment when administered to outpatients with bipolar disorder.

Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions.

OBJECTIVE: Steatohepatitis is a morphological pattern of liver injury that may be seen in alcoholic or nonalcoholic liver disease. This pattern may occur with obesity, diabetes, the use of certain drugs, or the cause may be idiopathic. The well-recognized histopathological features of nonalcoholic steatohepatitis (NASH) include hepatocellular steatosis and ballooning, mixed acute and chronic lobular inflammation, and zone 3 perisinusoidal fibrosis. Currently, there are no systems for grading necroinflammatory activity or for staging fibrosis as exist for various other forms of chronic liver disease. The purpose of this study was to develop such a grading and staging system and was based on review of liver biopsies from 51 patients with nonalcoholic steatohepatitis from Saint Louis University Health Sciences Center. METHODS: For determination of grade, 10 histological variables of activity were initially analyzed; an overall impression of mild, moderate, and severe was made and the variables considered to be most significant were used to develop the necroinflammatory grade. RESULTS: The histological lesions considered to be significant were: steatosis, ballooning, and intra-acinar and portal inflammation. A staging score was developed to reflect both location and extent of fibrosis. The fibrosis score was derived from the extent of zone 3 perisinusoidal fibrosis with possible additional portal/periportal fibrosis and architectural remodeling. Fibrosis stages are as follows: Stage 1, zone 3 perisinusoidal fibrosis; Stage 2, as above with portal fibrosis; Stage 3, as above with bridging fibrosis; and Stage 4, cirrhosis. CONCLUSION: We propose a grading and staging system that reflects the unique histological features of nonalcoholic steatohepatitis.

Ber-H2 (CD30) immunohistochemical staining in malignant melanoma.

Malignant melanoma can be included in the differential diagnosis of Hodgkin's disease, anaplastic large cell lymphoma, or embryonal carcinoma These malignancies express CD30, a marker of diagnostic value. A retrospective immunohistochemical study was undertaken to determine the frequency of immunoreactivity of Ber-H2 (anti-CD30 monoclonal antibody) in malignant melanoma Archival paraffin-embedded tissue from 24 primary and metastatic lesions was used. No Ber-H2 labeling was observed in the majority of the studied cases. Variable weak cytoplasmic staining was present in only one case. The findings are compared with the previous reports claiming frequent CD30 expression in malignant melanoma. We discuss issues pertaining to the interpretation of the Ber-H2 IHC staining in formalin-fixed, paraffin-embedded tissue.

Treatment of social phobia with gabapentin: a placebo-controlled study.

A randomized, double-blind, placebo-controlled, parallel-group study was conducted to evaluate the efficacy and safety of gabapentin in relieving the symptoms of social phobia. Sixty-nine patients were randomly assigned to receive double-blind treatment with either gabapentin (dosed flexibly between 900 and 3,600 mg daily in three divided doses) or placebo for 14 weeks. A significant reduction (p < 0.05) in the symptoms of social phobia was observed among patients on gabapentin compared with those on placebo as evaluated by clinician- and patient-rated scales. Results were similar for the intent-to-treat and week-2 completer populations. Adverse events were consistent with the known side effect profile of gabapentin. Dizziness (p = 0.05), dry mouth (p = 0.05), somnolence, nausea, flatulence, and decreased libido occurred at a higher frequency among patients receiving gabapentin than among those receiving placebo. No serious adverse events or deaths were reported. On the basis of these limited data, it seems that gabapentin offers a favorable risk-benefit ratio for the treatment of patients with social phobia. Further studies are required to confirm this effect and to determine whether a dose-response relationship exists.

Hepatic lipid peroxidation in hereditary hemochromatosis and alcoholic liver injury.

Studies in experimental animals have indicated that enhanced lipid peroxidation may play a role in the hepatic injury produced by iron overload or by excessive alcohol consumption. The aim of this study was to compare the formation of lipid peroxidation-derived aldehydes in the liver of patients with hereditary hemochromatosis (HH) and alcohol abuse. Liver biopsy specimens from 10 nondrinking patients with HH were evaluated. These patients were classified as having HH based on hepatic iron index or human leukocyte antigen identity with a known proband. All patients were homozygous for the Cys282Tyr mutation. In addition, 8 patients with alcoholic liver disease were examined, 2 of whom also had hemochromatosis. For comparison, 17 patients with liver diseases unrelated to iron overload or alcohol abuse were studied. Liver biopsy specimens were immunostained for protein adducts with malondialdehyde and 4-hydroxynonenal. Both malondialdehyde- and 4-hydroxynonenal-protein adducts were found from liver specimens of patients with HH and alcohol abuse in more abundant amounts than from patients in a control group. In alcoholics the adducts were primarily in zone 3, whereas in hemochromatosis staining had an acinar zone 1 predominance, which followed the localization of iron. The most abundant amounts of protein adducts were noted in patients with alcohol abuse plus iron overload. The data support the concept that both chronic alcohol use and iron overload induce hepatic lipid peroxidation. Through formation of reactive aldehydic products, excessive alcohol consumption and iron overload may have additive hepatotoxic effects.

Primary leiomyosarcoma of bone.

OBJECTIVE: This study describes radiographic and MR imaging features of primary leiomyosarcoma of bone. SUBJECTS AND METHODS: Twelve patients (five men and seven women, 39-79 years old) who were treated at two oncology centers for primary leiomyosarcoma of bone involving the femurs, tibia, ilium, and inferior pubic ramus were studied. None of the patients had preexisting disease or disease elsewhere at the time of diagnosis. Pathologic diagnosis was obtained in all patients. RESULTS: Radiographs of all patients showed a matrix that was exclusively osteolytic. In long bones (seven patients), the tumor had an average length of 11 cm (range, 7-17 cm) and revealed an elongated configuration. In the pelvis (five patients), the average length of the tumor was 10 cm (range, 4-15 cm). MR imaging confirmed an intramedullary lesion in all patients, with extension into the soft tissues in eight patients and no identifiable soft-tissue mass in the remaining four patients. Four of the five pelvic tumors had a prominent soft-tissue mass, whereas only four of the seven long bone lesions revealed a soft-tissue mass that was, in all instances, small. The tumor was hypointense on T1-weighted images and showed heterogeneous signal intensity on T2-weighted conventional and fast spin-echo sequences. We saw low signal intensity (short T2) in eight patients and homogeneous hyperintense signal intensity in one patient. In the remaining three patients, T2-weighted spin-echo sequences obtained with fat saturation showed high signal intensity (long T2) in the tumors. CONCLUSION: Primary leiomyosarcoma of bone is a rare tumor that on radiography reveals no matrix and on MR imaging reveals areas of T2 shortening in relation to fat on conventional and fast spin-echo sequences.

Diagnosis and management of appendiceal mucoceles.

Preoperative diagnosis of appendiceal mucoceles is rare. If untreated, one type of mucoceles may rupture producing a potentially fatal entity known as pseudomyxoma peritonei. The importance of diagnosing appendiceal mucoceles is highlighted through a case presentation of a woman who had an incidental finding of mucinous cystadenoma of the appendix during colonoscopic evaluation for occult gastrointestinal bleeding. A detailed review of the medical literature regarding appendiceal mucoceles is presented, with emphasis on the pathologic, clinical, radiologic, and evolving endoscopic features. Surgical options and prognosis are discussed.

Interpregnancy weight retention patterning in women who breastfed.

This study compares weight change in lactating women with an 18-month interpregnancy interval with woman who also breastfed but did not have an immediate subsequent pregnancy. Cases were women who breastfed an index infant for 6 months and subsequently became pregnant within 18 months (cases = 25), and the controls also breastfed an index infant for 6 months but had no ensuing pregnancy (controls = 20) within 18 months. The pattern of postpartum weight retention following the initial pregnancy was not statistically different in cases compared to the controls. However, following their ensuing subsequent pregnancy, cases were 1.3 kg heavier than their average weight after their baseline pregnancy (P = 0.02). The best predictor of this greater weight was their weight change during the interpregnancy interval (P = 0.03). Total weight gain during the gestational period of the subsequent pregnancy was not associated with the greater weight following the subsequent pregnancy. Likewise, estimates of the amount of energy as calories or physical activity levels were not significant predictors of this greater weight following the subsequent pregnancy. These findings suggest that monitoring of postpartum weight, even in breastfeeding women, is essential. These findings indicate that breastfeeding women begin the next postpartum interval weighing more than the amount observed in the initial postpartum period.

Role of calciotrophic hormones in calcium mobilization of lactation.

The postpartum period can be a time when profound changes in calcium metabolism and bone mineral density (BMD) occur, particularly in association with lactation. We investigated the hypothesis that calciotrophic hormones [1,25-dihydroxyvitamin D, 25-hydroxyvitamin D, and parathyroid hormone (PTH)] are different by lactation practice or hormone status [PTH-related peptide (PTHrP), estradiol, and prolactin] and have a potential role in the bone loss and recovery associated with lactation. 1,25-Dihydroxyvitamin D, 25-hydroxyvitamin D, PTH, femoral BMD, PTHrP, prolactin, estradiol, and bone turnover markers were measured at 2 wk and at 2, 4, 6, 12, and 18 mo postparturition in 115 postpartum women aged 20-40 y (parity: 0-1). Lumbar spine BMD was measured at 2 wk and at 6, 12, and 18 mo during the postpartum period. PTH, 1,25-dihydroxyvitamin D, and 25-hydroxyvitamin D concentrations were nonlinear across the 18-mo postpartum period. Between baseline and 18 mo postparturition, PTH and 1,25-dihydroxyvitamin D concentrations did not decline, while there was a substantial decline in 25-hydroxyvitamin D concentrations. PTH, 1,25-dihydroxyvitamin D, and 25-hydroxyvitamin D concentrations did not differ by lactation practice or by PTHrP, estradiol, or prolactin status. These classic calciotrophic hormones were not associated with concentrations of bone turnover markers or changes in BMD in lactating women. In summary, patterns of change in calciotrophic hormones (PTH, 1,25-dihydroxyvitamin D, and 25-hydroxyvitamin D) in the 18-mo postpartum period appeared to be independent of PTHrP, estradiol, prolactin, or lactation status and were not associated with bone turnover markers. These data do not support the hypothesis that these three calciotrophic hormones are a central part of the calcium mobilization associated with the bone loss of lactation.

Lactation and weight retention.

The effect of lactation on weight retention was investigated longitudinally, with data collected at 0.5, 2, 4, 6, 12, and 18 mo after parturition in 110 women aged 20-40 y who had been nulliparous or primiparous. At each evaluation women were categorized as fully breast-feeding, partly breast-feeding, or bottle-feeding including infants weaned to a bottle (bottle feeding/weaned). Postpartum weight retention was calculated by subtracting weight before pregnancy from weight at each evaluation. Lactation practices were found to be significantly associated (P < 0.05) with postpartum weight retention by longitudinal regression analysis. Women who bottle-fed their infants retained more weight over time than women who breast-fed their infants. Significantly slower rates of weight loss were observed when women ceased breast-feeding or switched from fully to partly breast-feeding. Weight retention over time was greater in women who were older, unmarried, or had greater weight gain during pregnancy (P < 0.05). A pattern of weight gain rather than weight loss was observed in unmarried women. Our findings suggest that lactation influences the pattern of postpartum weight retention; however, the effect of lactation on weight retention was sufficiently limited to warrant minimal emphasis on lactation as a means of minimizing postpartum weight retention.