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Obstructive jaundice. Diagnostic and therapeutic considerations.

The diagnostic approach to obstructive jaundice must be individualized on the basis of the sensitivity and specificity of the various procedures available. No single diagnostic approach is optimal in all patients. The physician must be guided by knowledge of the yield, complications, and cost of the tests available. In addition, interventional endoscopic and radiologic techniques add a new therapeutic dimension to the standard surgical approach.

Cholangiography↗

Microalbuminuria in diabetic and hypertensive patients and the general population--consequences of various diagnostic criteria--the Nord-Trøndelag Health Study (HUNT).

OBJECTIVE: The purpose of this paper was to study the prevalence of microalbuminuria (MA) in males and females of various ages by applying various diagnostic criteria. Three groups of subjects were studied: apparently healthy individuals; self-reported hypertensives; and diabetics. MATERIAL AND METHODS: A total of 9255 individuals (age > or =20 years), all of whom were identified from the large (n = 65 258) population-based Nord-Trøndelag Health Study (HUNT) performed in Norway between 1995 and 1997, delivered three morning urine samples for MA analysis. Of these individuals, 651 reported both diabetes and treated hypertension, 944 diabetes only and 5547 treated hypertension only. The remaining 2113 subjects without diabetes or treated hypertension were randomly selected. The albumin:creatinine ratio (ACR) was used as an expression of urine albumin excretion. RESULTS: Applying the classical definition of MA of ACR > or =2.5 mg/mmol in at least two out of three urine samples, the prevalence of MA in those with both diabetes and hypertension was 42.2% in males and 25.9% in females; corresponding values for those with diabetes only were 27.8% and 22.4%, for the hypertensives 19.3% and 11.5% and for the randomly selected sample 5.2% and 4.7%. The prevalence of MA increased strongly with increasing age for both genders in all subgroups. The prevalence of MA changed considerably when applying different cut-off values of ACR and at least one, two or three urine samples with ACRs above the cut-off value. CONCLUSIONS: This study, one of the largest cross-sectional screening studies of MA ever performed, clearly illustrates the consequences of applying different diagnostic criteria. The optimal cut-off levels of MA for the prediction of cardiovascular disease still remain to be properly defined, and more follow-up studies are therefore needed.

Adult↗

Affective disorders in the elderly: diagnostic and research considerations.

Although depressive disorders in the elderly represent a major public health concern by virtue of their high cost in human suffering, disability, and potential suicide, they have not been studied extensively, and specific criteria for diagnostic classification and optimal treatment are lacking. It seems likely that many of the affective syndromes in the elderly like senile melancholia, manic depressive illness, pseudodementia, and masked depression belong to the group of endogenous depressions, and can be identified by a constellation of clinical symptoms (endogenous or endogenomorphic profile), abnormal dexamethasone suppression test (DST) (at least 50%), and positive response to treatment with antidepressant medication. The rest are depressions reactive to psychogenic or sociogenic factors frequently presenting agitation as a dominant symptom, and finally there is a group of organic depressions due to underlying organic brain change, (i.e. senile dementia). It is possible that careful psychometric and psychiatric evaluation based on the symptom pattern, DST, and response to treatment would reveal reliable differences between pseudodementia and mild dementia and distinguish endogenomorphic from non-endogenomorphic depressions, respectively. The validity of such an approach remains to be demonstrated. Biological research in this area has provided valuable findings and should be the aim for the 1980s.

Aged↗

Novel P53 mutations detected by FAMA in colorectal cancers.

BACKGROUND: The aim of the study was to identify p53 gene mutations by FAMA (fluorescence-assisted mismatch analysis) in colorectal cancers. PATIENTS AND METHODS: Analytical scanning of the p53 gene (exons 5-9) was performed in colon cancer samples from 44 consecutive patients by FAMA. FAMA is a semiautomatic scanning approach based on the chemical cleavage of the mismatch in fluorescently labeled heteroduplex DNA, obtained from the combination of a normal and a mutated allele. FAMA has already shown optimal levels of diagnostic accuracy and sensitivity in detecting gene mutations (nucleotide substitutions, insertions/deletions) both at the germline and somatic level. The peculiar feature of FAMA is its ability to detect and localize mutations, by a redundant pattern of signals due to fluorescent DNA fragments generated by chemical cleavage. Moreover, previous data have demonstrated that normal contaminating DNA from stromal cells in the sample does not affect the sensitivity of the procedure, leading to the identification of the mutation even when the ratio mutant/normal allele is 10%. RESULTS: Eighteen mutations (12 missense, one nonsense, two deletions, three nucleotide substitutions at the level of the splice-junctions) and two polymorphisms were detected by FAMA in 17 patients (39%) and then confirmed by automated sequence analysis. Six of 18 mutations (33%) were not previously reported for colon cancer samples and two of 18 lesions (11%) were identified as novel p53 mutations. CONCLUSIONS: Analytical scanning of the p53 gene by FAMA in DNA from colon cancer samples provides a sensitive, accurate and specific diagnostic procedure for routine clinical application.

Colorectal Neoplasms↗

Estimation of restriction maps with known site order using a generalized linear model.

A generalized linear model with Gamma errors is used to estimate the coordinates of a restriction map when the site order is known. This can be conveniently programmed in a wide range of statistical packages (e.g. Genstat 5, Minitab, SAS), and gives maximum likelihood estimates with their associated optimal properties. Regression diagnostics allow the checking of assumptions and help to identify mis-specified, influential or discordant fragment lengths. A specific diagnostic for identifying fragment lengths causing reversal of restriction site order is derived. Exact 'fragment' lengths from DNA sequencing can be conveniently included in an approximate manner by giving them a larger weight than observed restriction fragment lengths. Two examples and the Genstat 5 codes used in their analysis are presented.

Algorithms↗

Biopsy-negative cardiac transplant rejection: etiology, diagnosis, and therapy.

PURPOSE OF REVIEW: As the frequency of cellular rejection after heart transplantation is decreasing, biopsy-negative episodes of rejection are being recognized more often. This article reviews the features of humoral rejection, which we believe is responsible for most episodes of biopsy-negative rejection. Hemodynamic compromise, in the absence of acute cellular rejection, called biopsy-negative rejection occurs in 10 to 20% of cardiac allograft recipients. These episodes of rejection are often more severe, and more difficult to treat, than classical acute cellular rejection. Histologic, immunofluorescence, and immunoperoxidase studies of endomyocardial biopsies from such patients often reveal intravascular macrophages, and immunoglobulin and complement deposition in capillaries, in the absence of lymphoid infiltrates, suggesting an antibody-mediated or humoral form of rejection. RECENT FINDINGS: Humoral rejection is associated with increased graft loss, accelerated transplant coronary artery disease, and increased mortality. Severely ill patients require intense therapy, which includes high-dose corticosteroids, cytolytic agents, intravenous heparin, intravenous gamma globulin, plasmapheresis, and/or antiproliferative agents. SUMMARY: Currently, our knowledge of the pathogenesis, diagnostic criteria, and optimal therapy for biopsy-negative rejection is incomplete, and evolving.

Biopsy↗

Current concepts of gunshot wound treatment: a trauma surgeon's perspective.

Trauma remains a significant and persistent public health problem, accounting for 90,000 deaths and 20 million people disabled annually. Current concepts of appropriate triage and emergency treatment of gunshot wounds are addressed from a trauma surgeon's perspective. Recent studies regarding prehospital transport policy, and acute diagnostic studies allow optimal treatment guidelines to be formulated. Specifically, rapid transport rather than prolonged on-scene treatment (including maneuvers such as formal thoracolumbar immobilization) should be given the highest priority. Also, routine arteriography (another time-consuming and invasive procedure) in the treatment of gunshot wounds to the extremity is no longer the standard of care.

Angiography↗

Spiral CT of the thorax in daily practice: optimization of technique.

Effective utilization of spiral computed tomography (CT) technology in imaging of the thorax requires an understanding of technical parameters that affect image and scan quality. This article discusses how operator-controlled scan parameters can be optimized to achieve diagnostic and cost-effective examinations appropriate for daily clinical practice.

Contrast Media↗

Accuracy of physicans' predictions of cholecystography results.

In the decision theory model of medical diagnosis and treatment, optimal choice of diagnostic tests requires accurate estimation of the probability that a given test will be positive. We assessed the ability of physicians to estimate the probability that a specific test (cholecystography) would be positive. For 102 patients, the predicted number of gallstone cases, 35.8, was significantly greater than the observed number, 15 (p less than 0.001), even though 13 of the 15 observed cases were patients with previous radiographic evidence of gallstones. The overestimation of probability of positive tests casts doubt on the correctness of decisions regarding selection of diagnostic tests when these decisions are derived from probability estimates based on intuition or expert opinion.

Adult↗

Nosocomial pneumonia.

Nosocomial pneumonia remains a major cause of morbidity, mortality, and significant hospital cost despite continued refinements in antimicrobial treatment, improved methods for diagnosis, and better supportive and preventive measures. While clinical experience is considerable, appreciation of the epidemiologic and pathogenic factors responsible for NP development and pathogen selection are limited, and consensus regarding optimal prevention and diagnostic and therapeutic strategies is lacking. This article reviews the recent literature with an emphasis on significance, pathogenesis, etiology, and therapy of nosocomial pneumonia.

Anti-Bacterial Agents↗

From King George to neuroglobin: the psychiatric aspects of acute intermittent porphyria.

The porphyrias are a heterogeneous group of inherited deficiencies in the heme biosynthetic pathway. Acute intermittent porphyria is both the most prevalent and most severe form of this illness. Psychiatric symptoms are part of the classic presentation of this disorder, and psychiatric patients have a higher rate of porphyria than the general population. Despite this, clinicians often fail to consider this diagnosis in the differential for recalcitrant psychosis or depression. Many patients are asymptomatic until exposed to certain medications, liver damage, or hormonal changes. Diagnosis requires a high index of suspicion and a thorough history, physical examination, and laboratory evaluation. The author reviews historical aspects, diagnostic features, and optimal treatment of acute intermittent porphyria, considers possible etiologies of its psychiatric symptoms, and provides two case histories as examples.

Journal Article↗

Villous adenocarcinoma of the colon and rectum: a clinicopathologic study of 36 cases.

Some colorectal adenocarcinomas show villous architecture with morphologic similarities to tubulovillous or villous adenomas. We reviewed 420 consecutive colorectal adenocarcinoma resection specimens and found that 95 tumors (23%) showed areas of villous architecture. Thirty-six tumors (8.6%) in 35 patients showed more than 50% villous architecture and were designated villous adenocarcinomas. Only 42% of the villous adenocarcinomas showed severe atypia and only 44% of the available pre-resection biopsies of these tumors were diagnosed as adenocarcinoma. Epithelial islands in desmoplastic stroma (EIDS) may be helpful in the diagnosis of these tumors. EIDS were found in 97% of the resection specimens for villous adenocarcinomas and none of 62 resection specimens for tubulovillous or villous adenomas. The presence of EIDS showed a 67% sensitivity, 100% specificity, and 100% predictive value in the diagnosis of villous adenocarcinoma in a blinded review of villous tumors. On review of the pre-resection biopsies of villous adenocarcinoma without a final diagnosis of adenocarcinoma, 40% showed EIDS. Clinical follow-up of the 35 patients with villous adenocarcinoma showed that only one died of colorectal adenocarcinoma (median follow-up, 46 months). This sole patient dying of colorectal adenocarcinoma showed a synchronous advanced stage of nonvillous adenocarcinoma at the time of diagnosis. Villous adenocarcinoma is a diagnostically challenging subset of colorectal adenocarcinoma, which appears to be associated with a favorable prognosis. Classifying these tumors as a special type of colorectal cancer may facilitate the development of diagnostic adjuncts and optimal treatment protocols.

Adenocarcinoma↗

The significance of Ureaplasma urealyticum as a pathogenic agent in the paediatric population.

PURPOSE OF REVIEW: Ureaplasma urealyticum is a frequent commensal in the lower genital tract of sexually active women. It may be transmitted perinatally from the colonized mother to her offspring, often resulting in prematurity and neonatal disease. The microorganism also sustains a causative role for infectious diseases in older children. RECENT FINDINGS: U. urealyticum infection can be diagnosed by culture, polymerase chain reaction, and the detection of specific antibodies. Neonatal infection has been implicated in various pathological conditions including pneumonia, chronic lung disease, central nervous system disorders, sepsis, osteomyelitis and even death. Older children may present with wheezing, pneumonitis, pertussis-like syndrome and different forms of arthritis. Large well-designed trials have demonstrated that the regular administration of antibiotics to vaginally colonized women are not beneficial in terms of preventing preterm labour. Macrolide-containing antibiotic regimens are, however, recommended for preterm premature rupture of the membranes. Erythromycin treatment of ureaplasma respiratory colonized premature infants shows no reduction in the incidence of chronic lung disease. Treatment of central nervous system infections, sepsis and arthritides includes tetracyclines, fluoroquinolones and anti-inflammatory agents, respectively. SUMMARY: This review covers recent evidence concerning the role of U. urealyticum as a pathogen during childhood. It also includes an evaluation of contemporary diagnostic techniques and optimal therapeutic approaches.

Female↗

Poisoning and epidemiology: 'toxicoepidemiology'.

1. There is little hypothesis-testing clinical research performed in toxicology. Randomized clinical trials are rare and most observational studies are performed on highly selected patients and are subject to marked bias. Thus, for many poisonings, our approach has been based almost entirely on deduction from known pharmacological/toxicological effects, generalizations from drugs within the same therapeutic class, animal data and case reports. This is also far from satisfactory, as many toxicological mechanisms are poorly understood and not related to the therapeutic class. 2. Although we need much better data to address the clinical and public health aspects of poisoning, there are many practical and ethical reasons why randomized clinical trials are difficult in this field. However, the scope for observational research, in particular population-based clinical epidemiology, is almost unlimited. The collection of data on human poisoning is facilitated because most non-fatal overdoses are admitted to hospital and by legal requirements to report to the coroner deaths that are due to poisoning. In the present article I argue that 'toxicoepidemiology', meaning the application of epidemiological methods to the problem of acute poisoning, is the best means we have of addressing deficiencies in our knowledge of poisoning. 3. Examples are given of a variety of observational research strategies, ranging from audit to meta-analysis, that may be applied to clinical toxicology. From coronial and clinical data obtained from reasonably well-defined populations, it has been possible to identify a number of previously unrecognized differences in the severity and spectrum of toxicity between and within drug classes. Also, the demographic risk factors for poisoning and the reproducibility, validity and optimal use of diagnostic and therapeutic interventions can be assessed. 4. The major limitations to the range of associations and interventions that may be studied are the need to achieve adequate power to study uncommon outcomes or poisonings and the ability to replicate findings at other centres using similar methodology. The expansion of data collection to other centres has the potential largely to overcome these obstacles.

Clinical Trials as Topic↗

Effect of heart rate on T wave alternans.

INTRODUCTION: T wave alternans (TWA) is a promising technique for detecting arrhythmia vulnerability. Previous studies in animals demonstrated that the magnitude of TWA is dependent on heart rate. However, the effects of heart rate on TWA in humans and the clinical relevance of this effect remain controversial. METHODS AND RESULTS: This was a prospective evaluation of pacing rate and monitoring lead configuration on TWA in subjects undergoing electrophysiologic study. Measurements of TWA were performed on 45 patients in the absence of antiarrhythmic drugs. Recordings were made in normal sinus rhythm and during atrial pacing at 100 and 120 beats/min. Sustained monomorphic ventricular tachycardia (VT) was induced in 29 patients with programmed stimulation. TWA in the vector magnitude lead increased with heart rate, independent of VT inducibility (0.4 +/- 0.7 microV, 1.6 +/- 1.9 microV, and 2.4 +/- 2.1 microV in sinus rhythm and at 100 and at 120 beats/min, respectively; P < 0.001). In addition, the diagnostic performance of TWA for inducible VT was dependent on heart rate (sensitivity 4%, 42%, and 65%, and specificity 100%, 93%, and 63% at 77, 100, and 120 beats/min, respectively). By analyzing orthogonal leads rather than the vector magnitude lead, the sensitivity is increased from 42% to 59% at 100 beats/min, but the specificity is reduced from 93% to 72%. CONCLUSION: These results indicate that TWA in humans is strongly dependent on heart rate with regard to both magnitude and diagnostic performance. The optimal heart rate for the measurement of TWA is between 100 and 120 beats/min and multiple leads should be monitored.

Cardiac Pacing, Artificial↗

Impact of transesophageal color flow Doppler echocardiography in current cardiology practice.

Of 3,480 patients who were referred for cardiac ultrasound evaluation, 230 patients (6.6%) underwent transesophageal echocardiography because the transthoracic study was not feasible, technically inadequate, or provided insufficient diagnostic information for optimal patient management. There were 149 inpatients and 81 outpatients. The majority (182 patients, 79%) had aortic or mitral disorders. In 166 patients (72%), transesophageal echocardiography played a significant role in patient management. Transesophageal echocardiography was most useful in evaluating diseases of the aorta (dissection, root abscess, or aneurysm), mitral prosthesis, complications of endocarditis, left atrial appendage thrombi, and in determining the cause of mitral insufficiency. Transesophageal echocardiography was useful in the evaluation of critically ill patients and those with severe lung disease.

Adolescent↗

Persistence of Cryptococcus neoformans in seminal fluid and urine under itraconazole treatment. The urogenital tract (prostate) as a niche for Cryptococcus neoformans.

The open questions of the persistence of Cryptococcus neoformans in the urogenital tract under antimycotic treatment can be examined under optimal mycological-diagnostic conditions only. The example of a case of cryptococcosis in an AIDS patient diagnosed and treated with itraconazole in the early secondary stage of cryptococcosis is used to discuss the problems of the persistence of Cr. neoformans involvement in the urogenital tract (prostate). Data from a ten-week follow-up study are presented and discussed. The observations made have shown that itraconazole is effective in all regions of the body, with the exception of the urogenital tract. In addition to clinical examinations, cases treated with itraconazole should be finally subjected to cultural examination of prostatic secretion and/or seminal fluid, to exclude the possible presence of a symptom-free involvement of the prostate by Cr. neoformans.

Acquired Immunodeficiency Syndrome↗

Immunosuppressive treatment of chronic periaortitis: a retrospective study of 20 patients with chronic periaortitis and a review of the literature.

BACKGROUND: Retroperitoneal fibrosis (RPF) and inflammatory aneurysm of the abdominal aorta (IAAA) are regarded as two manifestations of the same disease, termed "chronic periaortitis". OBJECTIVE: To determine the optimal therapeutic and diagnostic approaches to IAAA. METHODS: The outcome of medical immunosuppressive and surgical treatment of 20 patients was examined. Measurements of the C reactive protein (CRP) were compared with contrast enhanced imaging studies in the follow up of the patients. RESULTS: The diameter of the periaortic mantle and its contrast enhancement improved in 13/15 (87%) patients given immunosuppressive treatment for a period of more than 6 months. Strong contrast enhancement was associated with a substantial rise in CRP, but no correlation between the CRP value and thickness of the fibrotic mass was found, even at intraindividual follow up. CONCLUSIONS: Immunosuppressive treatment should be included in the first line treatment of patients with RPF and should be maintained long term. Imaging studies are better than CRP measurements in the evaluation of response to treatment.

Adult↗