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Natural history of primary sclerosing cholangitis and prognostic value of cholangiography in a Dutch population.

BACKGROUND: Median survival of patients with primary sclerosing cholangitis (PSC) has been estimated to be 12 years. Cholangiography is the gold standard for diagnosis but is rarely used in estimating prognosis. AIMS: To assess the natural history of Dutch PSC patients and to evaluate the prognostic value of a cholangiographic classification system. PATIENTS: A total of 174 patients with established PSC attending a university hospital and three teaching hospitals from 1970 to 1999. METHODS: Charts were reviewed for validity and time of diagnosis, concurrent inflammatory bowel disease, interventions, liver transplantation, occurrence of cholangiocarcinoma, and death. Follow up data were obtained from the charts and from the attending clinician or family physician. Median follow up was 76 months (range 1-300). The earliest available cholangiography was scored using a radiological classification system for the severity of sclerosis, developed in our institution. Survival curves were computed by the Kaplan-Meier method. Cholangiographic staging was used to construct a prognostic model, applying Cox proportional hazards analysis. RESULTS: The estimated median survival from time of diagnosis to death from liver disease or liver transplantation was 18 years. Cholangiocarcinoma was found in 18 (10%) patients. Fourteen patients (8%) underwent liver transplantation. Cholangiographic scoring was inversely correlated with survival. A combination of intrahepatic and extrahepatic scoring, together with age at endoscopic retrograde cholangiopancreatography, proved strongly predictive of survival. CONCLUSIONS: The observed survival was considerably better than reported in earlier series from Sweden, the UK, and the USA. Classification and staging of cholangiographic abnormalities has prognostic value.

Adult↗

Gynecologic imaging: comparison of transabdominal and transvaginal sonography.

The sonographic findings in 200 patients who underwent concurrent transabdominal and transvaginal pelvic ultrasound were reviewed. The sonographic techniques were compared for image quality, completeness of anatomic detail depicted, and unique diagnostic information. Transvaginal image quality was better in 79%-87% of scans; transabdominal image quality was better in 3%-5% of scans; images of both techniques were equally good in 10%-18% of scans. The techniques provided equivalent diagnostic information in 60%-84% of cases. Transvaginal sonography was particularly helpful when exclusion of ectopic pregnancy was the clinical concern. Individual organs and fine structures were better seen transvaginally, but the regional survey offered by the transabdominal full-bladder approach remains necessary to provide anatomic orientation, particularly when the patient has not been studied previously.

Adolescent↗

Phenobarbital does not prevent total parenteral nutrition-associated cholestasis in noninfected neonates.

Cholestasis associated with total parenteral nutrition (TPN) is a serious complication of this therapy for which there is no known treatment other than beginning enteral feeds. Phenobarbital is commonly used in other cholestatic disease states, but its benefit in this syndrome has not been demonstrated. We conducted a retrospective review of phenobarbital use in neonates receiving concurrent TPN. Thirty-one noninfected neonates were studied. They were without evidence of intrinsic liver disease at the institution of exclusive TPN therapy. For the purposes of this study, TPN-associated cholestasis was defined as a serum bilirubin in excess of 3 mg/dl at postnatal age of 3 weeks or more. Fourteen of the study infants received phenobarbital therapy for neurologic indications. Sixty percent of the phenobarbital-treated infants developed TPN-associated cholestasis, as compared to 33% of the untreated patients. Phenobarbital therapy was not effective in preventing TPN-associated cholestasis.

Cholestasis↗

Therapeutic management of hyperglycaemic hyperosmolar syndrome.

Hyperglycaemic hyperosmolar syndrome is a major acute complication of decompensated diabetes mellitus. It represents the second most common aetiology of diabetic coma and is associated with excess mortality. It is characterised by severe hyperglycaemia, hyperosmolality and dehydration in the absence of significant ketosis, afflicting principally middle-aged-to-elderly patients. Early clinical diagnosis and prompt treatment, consisting of fluid replacement, insulin therapy, restoration of electrolyte disturbances and management of concurrent illnesses may improve the outcome. This review provides an outline of the diagnostic approach of patients with manifestations of hyperglycaemic hyperosmolar syndrome and discusses the contemporary therapeutic recommendations.

Adult↗

Drug interactions with irbesartan.

Irbesartan is an angiotensin II receptor antagonist indicated for the treatment of patients with hypertension. Although irbesartan does not require biotransformation for its pharmacological activity, it does undergo metabolism via the cytochrome P450 (CYP) 2C9 isoenzyme and negligible metabolism by the CYP3A4 isoenzyme. The long term treatment of patients with hypertension is generally required for effective management of the disease, and the use of concurrent medications is usually inevitable. This paper reviews the drug and food interaction trials involving irbesartan that have been conducted to date. Based on the available literature, no significant interactions have been identified between irbesartan and hydrochlorothiazide, nifedipine, simvastatin, tolbutamide, warfarin, magnesium and aluminum hydroxides, digoxin or food. Fluconazole did increase the steady-state peak plasma concentration (by 19%) and area under the concentration-time curve (by 63%) of irbesartan, but these increases are not likely to be clinically significant. In summary, irbesartan has demonstrated minimal potential for drug or food interactions in trials conducted to date.

Antihypertensive Agents↗

A case of melanoma concurrent with progressive systemic sclerosis.

The association between progressive systemic sclerosis (PSS; scleroderma) and malignancy has been a controversial issue in the literature. The present report describes a rare case of concurrent malignant melanoma and PSS. A literature review suggests a possible connection between these two conditions.

Antineoplastic Combined Chemotherapy Protocols↗

Surgical management of left ventricular aneurysm and diffuse coronary artery disease: immediate and long term results in patients receiving three or more grafts.

Because little information is available concerning the outcome of surgery for left ventricular aneurysm when multiple concurrent coronary grafts are required, we have reviewed 35 consecutive patients undergoing aneurysm surgery and multiple (greater than or equal to 3) grafts between December 1973 and April 1984. There were 6 operative deaths (17%). All occurred amongst those (16) undergoing LV plication procedures with no deaths amongst those (19) undergoing aneurysm resection (p less than 0.01). Operative mortality was not influenced by preoperative functional status, left ventricular end diastolic pressure, completeness of revascularisation, endarterectomy (13 patients) or whether cold crystalloid cardioplegia or intermittent aortic cross clamp with ventricular fibrillation was used. Overall 5-year actuarial survival was 70% with survival beyond surgery being 84% to 5 years and independent of the type of aneurysm procedure. Of the survivors, 16 were improved by 1-3 functional classes, 3 were unchanged and one was worse. Surgery in this group of patients offers the prospect of good symptomatic improvement and survival figures which at least equal the results of less complex ventricular aneurysm surgery and exceed those reported for medical management.

Adult↗

Gemcitabine plus radiation therapy in the treatment of locally advanced non small-cell lung cancer.

For stage III non small-cell lung cancer, there is a need for better systemic, as well as locoregional, control of the tumor. In an attempt to enhance this locoregional control, systemic chemotherapy has been given currently with radiation therapy. Gemcitabine, a novel deoxycytidine analogue, has been shown to be a potent radiosensitizer. This review focuses on the studies using gemcitabine concurrently with radiation therapy in the treatment of locally advanced non small-cell lung cancer.

Journal Article↗

AIDS-Related Malignancies.

OVERVIEW OF MALIGNANCY IN PATIENTS WITH AIDS: Despite the advent of highly active antiretroviral therapy, the incidence of human immunodeficiency virus (HIV)-associated malignancies has not decreased. The United States Centers for Disease Control (CDC) has determined that Kaposi's sarcoma, non-Hodgkin's lymphoma (including primary central nervous system lymphoma), and cervical carcinoma define the acquired immune deficiency syndrome (AIDS). Some literature reports include Hodgkin's disease, anal carcinoma, lung cancer, and non-melanomatous skin cancers as ones commonly found in people infected with HIV. The oncologist is further challenged treating a patient with malignancy whose malignancy is complicated by a concurrent compromised marrow function. This article will review the clinical presentation and current treatment for the HIV-associated malignancies and selected other tumors in the HIV-infected patient. Furthermore, HIV-associated myelosuppression is a common problem in antiviral-undertreated or antiviral-resistant patients.

Journal Article↗

Wound healing in acute spinal cord injury: effect of anticoagulation.

Medical records were surveyed to test the impression that anticoagulation therapy administered to patients hospitalized for acute spinal cord injury impaired wound healing. Records for 25 patients with 26 wounds, located over the sacrum (21), thigh (two), occiput, heel, or buttock (one each), were reviewed. Among 11 wounds not associated with concurrent anticoagulation therapy, healing was delayed beyond 75 days in two patients. Among 15 wounds associated with anticoagulation therapy (heparin or heparin followed by coumarin derivatives), healing was delayed more than 75 days in nine patients (chi 2 = 4.53, p less than 0.05). This association of anticoagulation therapy with impaired wound healing in patients with an acute spinal cord injury suggests that this factor should be considered in future studies of wound healing.

Adolescent↗

Eosinophils in equine uterine cytology and histology specimens.

In a review of specimens from 80 mares with concurrently collected endometrial biopsy and cytology preparations, eosinophils were found in 33 specimens from 27 mares. In 22 of 27 mares, there were conditions predisposing to pneumovagina, which presumably led to pneumouterus. Thirty-two of the 80 mares also had conditions predisposing to pneumovagina but no eosinophils in the uterine specimens. Experimental introduction of air into the uterus of 3 mares resulted in eosinophils in their uterine specimens.

Air↗

Pancytopenia due to vitamin B12 deficiency associated with Graves' disease.

Pancytopenia has a broad differential diagnosis, which can be narrowed depending on the cellularity of the bone marrow. The authors describe a complex patient with a history of Graves' disease who presented with pancytopenia, initially suspected of being due to aplastic anemia. He was later diagnosed with Vitamin B12 deficiency as a result of pernicious anemia. The potentially striking hematologic effects of cobalamin deficiency and the autoimmune basis for concurrent Graves' disease and pernicious anemia are reviewed.

Biopsy, Needle↗

Outcome of clozapine therapy for elderly patients with refractory primary psychosis.

OBJECTIVE: The objective was to analyze outcome of clozapine therapy in elderly patients with treatment refractory primary psychosis. DESIGN: This was an open-label clozapine trial in elderly patients. Patient psychopathology was assessed before and after clozapine therapy. SETTING: A psychiatry service at a large urban/suburban Veterans Administration Medical Center. PATIENTS: Inpatients and outpatients age 65 years or older with primary psychotic disorders established to be resistant to conventional antipsychotic therapy (Kane et al., 1988). Ten patients met study inclusion criteria out of a total of 134 patients receiving clozapine at the Cleveland VAMC (7.5%). Mean age of the group was 70.6 years. MEASURES: Patients were rated with the Brief Psychiatric Rating Scale (BPRS; Overall and Gorham, 1962). Additional data on patient demographics, comorbid non-psychiatric diagnoses and concurrent psychotropic medication were collected via chart review. RESULTS: Mean clozapine dosage was 204 mg/day for a mean duration of 430 days. 7/10 patients had some degree of clinical improvement and 3/10 patients had significant improvement documented by BPRS change of 20% or greater. Patients had a mean of 1.4 comorbid physical illnesses, which were not worsened by clozapine therapy. 4/10 patients discontinued clozapine therapy due to adverse effects or inability to comply with bloodwork; however; only 2/10 were truly treatment intolerant. CONCLUSIONS: Clozapine is a useful alternative treatment option for elderly individuals with refractory primary psychosis. As in younger patients, inability to tolerate drug-related adverse effects or weekly bloodwork may lead to drug discontinuation.

Aged↗

Benzodiazepine use in pregnancy and major malformations or oral cleft: meta-analysis of cohort and case-control studies.

OBJECTIVE: To determine if exposure to benzodiazepines during the first trimester of pregnancy increases risk of major malformations or cleft lip or palate. DESIGN: Meta-analysis. SETTING: Studies from 1966 to present. SUBJECTS: Studies were located with Medline, Embase, Reprotox, and from references of textbooks, reviews, and included articles. Included studies were original, concurrently controlled studies in any language. INTERVENTIONS: Data extraction and quality assessment were done independently and in duplicate. MAIN OUTCOME MEASURES: Maternal exposure to benzodiazepines in at least the first trimester; incidence of major malformations or oral cleft alone, measured as odds ratios and 95% confidence intervals with a random effects model. RESULTS: Of over 1400 studies reviewed, 74 were retrieved and 23 included. In the analysis of cohort studies fetal exposure to benzodiazepine was not associated with major malformations (odds ratio 0.90; 95% confidence interval 0.61 to 1. 35) or oral cleft (1.19; 0.34 to 4.15). Analysis of case-control studies showed an association between exposure to benzodiazepines and development of major malformations (3.01; 1.32 to 6.84) or oral cleft alone (1.79; 1.13 to 2.82). CONCLUSIONS: Pooled data from cohort studies showed no association between fetal exposure to benzodiazepines and the risk of major malformations or oral cleft. On the basis of pooled data from case-control studies, however, there was a significant increased risk for major malformations or oral cleft alone. Until more research is reported, level 2 ultrasonography should be used to rule out visible forms of cleft lip.

Abnormalities, Drug-Induced↗

Intestinal aganglionosis associated with the Waardenburg syndrome: report of two cases and review of the literature.

The authors report two cases of the rare concurrence of intestinal aganglionosis and Waardenburg syndrome in Japanese infants. The patients were a 1-month-old girl and a 3-month-old boy at diagnosis, and both of them had either short segment or ultra-short segment aganglionosis. A review of 48 cases in the literature showed that the extent of the aganglionic segment is quite variable, from nearly total to ultra-short. The clinical features of aganglionosis in Waardenburg syndrome would appear to bear similarity in sex ratio and the extent of aganglionosis with those of Hirschsprung's disease associated with Ondine's curse, another type of neurocristopathy.

Comorbidity↗

Concurrent primary intracranial tumours of different histogenesis.

The occurrence of intracranial tumours of diverse histogenesis can be considered occasional. In a careful survey of the literature we have encountered 63 cases of concurrent intracranial tumours: we report five personal observations, too. This review raises the question as to whether the conjoint occurrence of two intracranial tumours is purely coincidental. The statistical analysis of the cases of concurrent intracranial tumours, and the comparison between the frequency found for each different tumour when it is solitary and when it is coincident in a same patient, suggests that a casual connection can be found between tumours of diverse histogenesis.

Astrocytoma↗

Pregnancy outcome in gestational diabetes.

OBJECTIVE: To assess maternal and neonatal outcomes of gestational diabetes mellitus (GDM) following glycemic screening and diabetic management, with special focus on concurrent GDM and pre-eclampsia. METHODS: A retrospective chart review of 782 women diagnosed with and treated for GDM at a Chinese university teaching hospital. Data on maternal and neonatal outcome, glycemic control, concurrent pre-eclampsia, and diabetic management were collected and analyzed. RESULTS: The incidence of GDM was 3.8%. Of the affected women, 62.9% were managed with diet only and the remainder received insulin treatment. Overall, 80.7% had good glycemic control. Poor glycemic control and concurrent pre-eclampsia correlated with maternal and neonatal complications. CONCLUSION: Aggressive management for tight glycemic control improves maternal and neonatal outcomes in women with GDM.

Adult↗

Histopathology of bone marrow.

As a major hematopoietic and lymphoid organ, morphological evaluation of the bone marrow is an important component of toxicity or safety assessment studies. While definitive characterization of bone marrow lesions often requires cytological aspirates or smears, assessment of histological bone marrow sections provides information regarding tissue architecture and hematopoietic status that is relevant for the detection of direct or indirect responses to chemical exposure. A variety of lesions have been observed in bone marrow. For example, lesions involving disturbances in growth, degenerative changes, inflammatory changes and neoplasia have been described. Lesions identified in hematoxylin and eosin-stained sections typically represent changes in the hematopoietic cell lineage and/or stromal cells since definitive identification of lymphoid cells is difficult except in cases of lymphoma. This review provides a descriptive and pictorial representation of a wide range of bone marrow lesions. Since large animal-to-animal variation may exist and there can be collection site- and age-related differences, it is imperative that the pathologist reviews all potential treatment-related findings against appropriate concurrent controls.

Animals↗