Elevated liver enzymes of unknown etiology

Elevated liver enzymes are a frequent clinical problem of varying significance. In otherwise healthy individuals the most frequent causes of elevated liver enzymes are toxins such as alcohol and drugs. In this situation, further studies are usually not needed; it is sufficient to control the relevant parameters after abstinence from alcohol or withdrawal of the drug(s). In patients with known, suspected or unknown nonhepatic diseases, elevated liver enzymes can be caused by cardiovascular diseases, obesity, endocrinopathies, infectious diseases, malignancies, collagen disorders, sarcoidosis and other diseases. In this situation, sonography or liver histology frequently will be diagnostic, revealing the cause of the underlying disease as well as of the elevated liver enzymes.     

Acute pancreatitis of unknown etiology in the elderly

OBJECTIVE: The incidence of acute pancreatitis in the elderly patient is increasing, and a significant number of such patients have no clearly defined etiology of their pancreatitis. To delineate the role of early organ failure versus progressive pancreatic disease in the morbidity and mortality, the authors' experience with patients older than 60 years with acute pancreatitis was reviewed. SUMMARY BACKGROUND DATA: As many as 30%-40% of elderly patients with acute pancreatitis have an unclear etiology and such patients have high rates of early organ failure and death. While some authorities have shown that pre-existing disease in these elderly patients did not contribute to subsequent morbidity, others have demonstrated that poor outcome was related to co-existing medical illness. METHODS: Their review of acute pancreatitis in the elderly was grouped into known and unknown etiology patients. Various parameters such as morbidity, mortality and length of stay were then compared between the two groups. Severity of organ failure and acute pancreatitis on admission were both graded and attempts made to correlate this severity with subsequent outcome. RESULTS: Unknown etiology patients had a greater number of Ranson's criteria (3.5 +/- .44 vs. 2.4 +/- .18) (p < 0.02), higher morbidity (48% vs. 22%) (p < 0.05), higher mortality (24% vs. 8.3%), and more SICU days (4.4 +/- 1.3 vs. 1.6 +/- .44) (p < 0.05) when compared with the known etiology group. Duration of symptoms, admission hypotension, and Ranson's criteria were unsuccessful in predicting mortality. Functional status of the various organ systems on admission did predict subsequent mortality. CONCLUSIONS: Elderly patients with acute pancreatitis of unknown etiology present with a more severe disease, have higher morbidity and longer SICU stays, and appear to have greater compromise of organ function. Organ function compromise correlates with mortality and appears more significant than severity of pancreatic disease. Aggressive support of such organ systems may be beneficial in the management of these patients.     

Transrectal prostate puncture biopsy in ambulatory care

One may not rely solely on serum lithium levels to detect or prevent lithium intoxication. A review of the reported cases of serious lithium intoxication despite "therapeutic" blood levels of lithium is presented, along with a discussion of possible explanations for the phenomenon. Possible alternate means of following a patient on lithium carbonate are discussed.     

Immunological abnormalities in patients with etiology unknown sensorineural hearing loss

An immunological study was carried out in 50 patients with etiology unknown sensorineural hearing loss, including the following: 12 low tone deafness, 7 sudden deafness, 8 unilateral deafness, 7 idiopathic bilateral progressive sensorineural hearing loss and 14 other bilateral sensorineural hearing loss. Twenty-five out of 50 of the cases demonstrated immunological abnormalities. A full array immunological tests were performed with the following results. High immnunoglobulin titers showed in 18 out of 50 cases. Six cases were positive for antinuclear antibody. The anti-DNA antibody assay revealed high titers in 2 cases. Also, anti-rheumatoid factor antibody assay showed high titers in 6 cases while abnormal values of complements in serum were detected in 6 cases, though an immune complex was demonstrated in only one case. Also, it was noted that six patients with immunological abnormalities have autoimmune diseases. The above results indicated that some cases of etiology unknown sensorineural hearing loss may have an immunological link.     

An unknown etiology of fetal ascites: acute intestinal intussusception

BACKGROUND: Intussusception is a frequent diagnosis during the first year of life. However, it is an uncommon and very rare pathology in neonates and premature infants. CASE REPORTS: Two full term neonates presented an antenatal intussusception associated with fetal ascites; another premature infant developed an intussusception at the age of 15 days. In the three cases the diagnosis of intussusception had only been established during the laparotomy. A recent review of the literature revealed 13 cases of antenatal intussusception, one of these being associated with fetal ascites. CONCLUSION: The differential diagnosis of fetal ascites should always include intussusception. Early recognition of this pathology and prompt surgical action would avoid fatalities.     

Use of flumazenil in the diagnosis and treatment of patients with coma of unknown etiology

OBJECTIVES: To evaluate the use of single-dose flumazenil in the diagnosis of coma of unknown etiology, and of continuous flumazenil infusion in the treatment of benzodiazepine-induced coma. DESIGN: Prospective study. SETTING: Emergency room and general medicine ward of a teaching hospital. PATIENTS: A total of 42 comatose adults in whom metabolic, neurologic, or traumatic causes of coma were excluded. INTERVENTIONS: a) Intravenous bolus injections of 0.25 mg flumazenil were given at 1-min intervals, either until improvement by two coma grades or a total dose of 2.0 mg was reached. b) Loading doses as in (a) followed by a maintenance infusion administered as long as indicated by repeated coma grade evaluation. MEASUREMENTS AND MAIN RESULTS: a) Of 34 patients, 28 received only the flumazenil loading dose responded promptly. Twenty-one of 25 available urine samples of the responding patients contained only benzodiazepine metabolites. Four urine samples contained benzodiazepines in combination with other drugs. Six patients did not respond to the flumazenil loading dose. The urine of three patients contained a combination of benzodiazepines and another coma-exerting drug; the remaining three were negative. A total of 24 patients, who initially responded to flumazenil loading, deteriorated to their previous coma state and were admitted to the general medical ward. Six (25%) patients developed complications related to hospitalization and their bedridden state. b) Eight other patients, who deteriorated after an initial loading dose, received a second iv bolus of flumazenil, followed by maintenance infusions over 5 to 24 hrs. Their hospital course was uneventful. CONCLUSIONS: These findings indicate that flumazenil is safe and effective in the diagnosis of benzodiazepine-induced coma. Furthermore, the use of continuous flumazenil maintenance infusion is of considerable therapeutic value in patients who exhibit deterioration after initial response to the single loading dose.     

Chronic enteropathy of unknown etiology in patients with AIDS. An analysis of 40 cases

BACKGROUND: Data about the etiology of chronic enteropathy in AIDS patients are scarce and are very dependent upon the geographical area. The aim of this study was to detect microorganisms potentially associated with chronic enteropathy in AIDS patients with diarrhoea for more than one month, and initial negative routine stool bacterial cultures and examinations for ova and parasites. The degrees of associated intestinal malabsorption and immunodeficiency were also analysed. PATIENTS AND METHODS: Forty consecutive patients were recruited from January 1993 to December 1994. The following studies were performed: Intestinal absorption tests (d-xylose and 14C-triolein), CD4/CD8 cell counts, microbiological studies (standard stool cultures for detection of bacteria and examinations for ova and parasites including the detection of Enterocitozoon bieneusi spores by the Weber's stain), upper gastrointestinal endoscopy or colonoscopy with intestinal biopsies and blood cultures for CMV and mycobacteria. RESULTS: The median duration of diarrhoea was 4 months and the mean weight loss was 8.4 kg. Ninety percent of patients had less than 0.1 x 10(9) CD4+ cells/l, with a mean CD4+ cell count of 0.035 x 10(9)/l. Malabsorption was found in 84% of patients. An etiological diagnosis of chronic enteropathy was reached in 60% of the patients. The yield of pathological examination was 37% and the microbiological test using samples of faeces and blood were positive in 45% and 20% of cases respectively. The most frequently identified microorganisms were CMV (10 cases), E. bieneusi (9), enterobacteria (8), Cryptosporidium parvum (5), Leishmania donovani (2). Patients with enteropathy caused by E. bieneusi had lower count of CD4 cells (p = 0.005) and with higher serum levels of alkaline phosphatase (p = 0.02) than patients with CMV enteropathy. CONCLUSIONS: Stool Weber's stain and CMV and mycobacterial blood cultures should be added to the standard work-up diagnosis in patients with chronic diarrhoea and a CD4+cells count below 0.1 x 10(9) l. Upper and/or lower gastrointestinal endoscopies with intestinal biopsies should be performed only in patients with persistent diarrhea without microbiological diagnosis or a lack of response to treatment.     

Extensive mesenteric inflammatory veno-occlusive disease of unknown etiology after primary cytomegalovirus infection: first case

We report a young man who, shortly after a primary cytomegalovirus infection, presented with signs of intestinal ischemia requiring surgical intervention. The resected specimen of small bowel showed striking features of extensive phlebitis and venulitis affecting virtually all of the veins of the small intestine and mesentery. Although he had had a recent primary cytomegalovirus viremia, we could not identify any evidence of cytomegalovirus in the small bowel. He was not infected with HIV. The entity we describe is different from the recently reported mesenteric inflammatory veno-occlusive disease. The clinicopathologic entity represented by our patient's disease was heretofore unrecognized.     

Mitochondrial DNA mutation at nucleotide 1555 in a patient with bilateral sensorineural hearing loss of unknown etiology

A mitochondrial DNA mutation at nucleotide 1555 in the ribosomal RNA gene was recently reported as a cause of maternally inherited non-syndromic sensorineural deafness. We assumed that the 1555 mutation is also associated with sporadic non-syndromic deafness and screened for the mutation in seven randomly selected sporadic cases with bilateral sensorineural hearing loss of unknown etiology. The mutation was found in one patient, who first noticed hearing loss when she was in her early teens with subsequent gradual progression. The results suggest that the 1555 mutation may contribute to the etiology of idiopathic bilateral sensorineural hearing loss in some cases.     

Bone marrow biopsy in the diagnosis of fever of unknown origin in patients with acquired immunodeficiency syndrome

BACKGROUND: Fever is commonly observed in patients with human immunodeficiency virus (HIV) disease and frequently eludes diagnosis. The role of bone marrow biopsy in the diagnosis of fever of unknown origin in patients infected with HIV remains controversial. PATIENTS AND METHODS: One hundred twenty-three consecutive patients with 137 episodes of fever lasting 10 or more days without diagnosis after 1 week of hospitalization were evaluated by bone marrow biopsy. RESULTS: Overall, a specific diagnosis was achieved in 52 episodes by means of culture and histopathological examination (diagnostic yield, 37.9%). Three types of disease were found: mycobacterial infections (n = 36, 69% of documented episodes), including 18 patients with disseminated tuberculosis and 14 with Mycobacterium avium-intracellulare complex infections; non-Hodgkin lymphomas (n = 12, 23%); and visceral leishmaniasis (n = 4, 8%). Although bone marrow cultures were more sensitive than microscopic examination with special stains for the diagnosis of mycobacterial infections, the pathological examination of bone marrow led to a more rapid diagnosis of disease. In addition, the histopathological examination of bone marrow alone led to the diagnosis of a specific condition in 43 episodes (31.3% of all episodes). CONCLUSIONS: Bone marrow biopsy is a useful procedure for the diagnosis of fever in patients with advanced HIV disease, particularly in areas where tuberculosis and leishmaniasis are prevalent. Involvement of the marrow may be the first indication of the existence of extranodal non-Hodgkin lymphoma. For Mycobacterium avium-intracellulare complex infection, blood cultures were more sensitive than bone marrow biopsy.     

Serum markers for the staging of disease activity of sarcoidosis and other interstitial lung diseases of unknown etiology

We analyzed transformation of the interphase microtubular cytoskeleton into the prophase spindle and followed the pattern of spindle axis determination. Microtubules in endosperm of the higher plant Haemanthus (Scadoxus) were stained by the immunogold and immunogold silver-enhanced methods. Basic structural units involved in spindle morphogenesis were "microtubule converging centers." We emphasized the importance of relative independence of chromosomal and microtubular cycles, and the influence of these cycles on the progress of mitosis. Cells with moderately desynchronized cycles were functional, but extreme desynchronization led to aberrant mitosis. There were three distinct phases of spindle development. The first one comprised interphase and early to mid-prophase. During this phase, the interphase microtubule meshwork radiating from the nuclear surface into the cytoplasm rearranged and formed a dense microtubule cage around the nucleus. The second phase comprised mid to late prophase, and resulted in the formation of normal (bipolar) or transitory aberrant (apolar or multipolar) prophase spindles. The third phase comprised late prophase with prometaphase. The onset of prometaphase was accompanied by a rapid association of microtubule converging centers with kinetochores. In this stage aberrant spindles transformed invariably into bipolar ones. Lateral association of a few bipolar kinetochore fibers at early prometaphase established the core of the bipolar spindle and its alignment. We concluded that (1) spindle formation is a largely independent microtubular process modified by the chromosomal/kinetochore cycle; and (2) the initial polarity of the spindle is established by microtubule converging centers, which are a functional substitute of the centrosome/MTOC. We believe that the dynamics of microtubule converging centers is an expression of microtubule self-organization driven by motor proteins as proposed by Mitchison [1992: Philos. Trans. R. Soc. Lond. B. 336:99].     

Cytological study of the puncture biopsy specimens of the Douglas' pouch for early diagnosis of ovarian tumors

The conducted studies indicated the diagnostic opportunities of a cytologic analysis of exudates and smears from the Douglas space in patients with a suspicion to ovarian tumor. Tumor cells may be present in the peritoneal cavity not only in different stages of malignant ovarian tumors, but also in secernent and proliferating cystadenomas. A correlation between the peritoneal cell content in patients with different forms of ovarian neoplasms and press-smears from the dissected surface of the removed tumors and histological sections indicated the morphological identitiy of tumor elements and enabled the determination of the cytological criteria for the differential diagnosis of ovarian tumors prior to surgical intervention.