Techniques for rapid quantitative assessment of activity levels in small-group tutorials

OBJECTIVE: To describe a case of pemoline-induced liver failure resulting in liver transplantation. CASE SUMMARY: A 9-year-old white boy, diagnosed with attention deficit/hyperactivity disorder (ADHD) and treated with pemoline, developed signs and symptoms of liver failure. Pemoline therapy was discontinued, but the patient's liver function continued to decline. Ultimately, a liver transplantation was required. DISCUSSION: Pemoline, an agent used in ADHD treatment, has been associated with hepatotoxicity with the majority of cases occurring in pediatric patients. To our knowledge, this is the second reported case of pemoline-induced liver failure resulting in liver transplantation. The mechanism of action remains unclear, with several hypotheses being postulated including hypersensitivity reactions, dose-related phenomena, and autoimmune-mediated reactions. CONCLUSIONS: With increasing evidence linking pemoline to liver failure, this agent should not be considered first-line therapy for ADHD. Prior to initiating therapy, baseline liver function tests should be obtained and closely monitored, and parents and patients should be educated on the signs and symptoms of liver toxicity.     

Digitalis intoxication: specifity and significance of cardiac and extracardiac symptoms. part II. Patients with extracardiac symptoms of digitalis intoxications (author's transl)

In 1148 cases the serum digoxin concentration (SDC) was correlated with the extracardiac signs of digitalis intoxication. There is a considerably overlap of SDC levels of patients with and without extracardiac signs of toxicity even though the mean SDC's of these two groups differ significantly. An increasing percentage of clinical intoxicated patients with increasing SDC levels was found at digoxin concentrations of 2.0 ng/ml and higher. At lower SDC levels patients with and without extracardiac signs of digitalis intoxication did not differ significantly in their mean SDC but in mean age and in mean creatinine concentration indicating that at least part of the symptoms in these patients might be due to a more severe illness. We could show that many of the extracardiac signs of digitalis intoxication are also seen in patients with impaired kidney function at low SDC levels and may lead to a wrong diagnosis. The most common complaint in patients with SDC's of 2.0 ng/ml and more is nausea (39.4%), followed by tiredness (30.4%), dizzyness (23.7%), vomiting (23.1%), headache (16.0%), visual disturbances (13,5%), colour (yellow) seeing (6;7%), diarrhea (4.2%) and severe neuro-psychiatric disturbances (3.8%). In patients with digitalis-induced arrhythmias the sequence of symptoms is the same only with a somewhat higher percentage rate. Only about one half of the patients with digitalis-induced arrhythmias and SDC values up to 2.5 ng/ml showed also extracardiac signs of intoxication. Therefore these signs are not to be taken as early symptoms of digitalis intoxication. Divided into subgroups (patients with/without digitalis-induced arrhythmias, patients with SDC values of more/less than 2.0 ng/ml) the patients with and without extracardiac signs of digitalis toxicity are compared with each other in regard to: mean body height and weight, concentration of digoxin, potassium and creatinine, digoxin dosage and mean age. The greatest differences were found between patients with combined cardiac and extracardiac signs of intoxication and patients with neither cardiac nor extracardiac signs of intoxication: These intoxicated patients are of significantly higher mean age and lower body weight, their mean concentration of digoxin and creatinine and the digoxin dosage administered are significantly greater, but there is no significant difference in potassium concentration. An important group of patients, namely the elderly with impaired kidney function, are especially prone to develop digitalis intoxication. In this group, however, the extracardial symptoms are of little benefit in the diagnosis of digitalis intoxication. In these patients rhythm disturbances and intoxication-like symptoms are frequently caused by other reasons. In most cases the SDC value can clarify the diagnosis without withdrawal of the drug.     

Cerebral embolism caused by a right ventricular pacemaker electrode perforated into the left atrium

The authors present a new, unusual side effect due to retained pacemaker lead. The free tip of the lead caused cerebral embolism by perforating the interatrial septum. Transoesophageal echocardiographic study showed the lead crossing the interatrial septum. The total abnormal course of the lead was demonstrated by lateral X-ray picture. Diagnostic and therapeutic approaches regarding retained leads in malposition are also discussed.     

Long-term follow-up study on drop-out TMD patients with self-administered questionnaires

Although patient attrition might be a serious threat to the validity of treatment-outcome studies on temporomandibular disorders (TMD), studies on TMD patient attrition are scarce. Of the 1405 consecutive TMD patients examined in a recent 10-year period, 367 (26.1%) drop-out patients or patients identified with a control group were sampled. A mailed questionnaire failed to reach 41 patients, and 203 (62.3%) were returned. The questionnaire elicited information on reasons for dropping out, changes in symptoms, treatment received in other clinics after dropping out, present treatment needs, and current signs and symptoms. Dropouts were divided into two groups: (1) those who failed to show up for their first scheduled appointment after the clinical examination; (2) those who failed to complete treatment. A group of patients who were judged by the examiner not to need treatment were included as a control group. The main reasons for dropping out were environmental obstacles, perceived improvement of the disease, and dissatisfaction with services. Only 21.7% considered themselves to be in need of treatment, and only 10.3% had visited other clinics after dropping out. Only 8.9% complained of the continued aggravation of symptoms, whereas 57.6% reported improvement. In addition, pain, dysfunction, and daily activity limitation tended to improve with time, although temporomandibular joint noise tended to persist. These results suggest that TMD signs and symptoms tend to decrease in patients after dropping out, and that the natural fluctuation of TMD signs and symptoms should be taken into consideration when treating TMD.     

Effect of compounds with antibacterial activities in human milk on respiratory syncytial virus and cytomegalovirus in vitro

In differential diagnosis of a delir also adverse effects of medicaments have to be taken into account beside other causes. We report a case of an agitated delir with nocturnal disturbance of consciousness, confusion, restlessness and sleeplessness. This delir existed exclusively during the therapy of a cutaneous herpes zoster with zovirax-pills which can only be explained by a causal connection--after exclusion of other causes. As a so far undescribed predisposition for neurotoxicity of oral therapy with acyclovir signs of vascular encephalopathy were found in the patient's cranial magnetic resonance imaging. The central nervous side effects of acyclovir were summarized shortly.     

Inhibitors of mitochondrial energy production prevent DNA internucleosomal fragmentation in thymocytes

We describe a case of multiple hepatic pyogenic abscesses with an unusual presentation. The typical signs and symptoms of fever and pain in the right upper quadrant were absent. Instead, the chief complaint was muscle weakness and myalgias accompanied by weight loss. Findings from an ultrasonogram of the abdomen revealed multiple hepatic lesions consistent with metastases. Hence, the initial presumptive diagnosis was metastatic malignancy with unknown primary tumor. It was only when purulent material was unexpectedly encountered when a needle biopsy was performed that the true diagnosis of pyogenic liver abscess was recognized. While liver abscess is rare, it should not be forgotten in the differential diagnosis for multiple hepatic lesions seen on imaging studies.     

Fatal neonatal liver failure and mitochondrial cytopathy (oxidative phosphorylation deficiency): a light and electron microscopic study of the liver

Mitochondrial cytopathies are multisystemic disorders of extremely variable expression due to a deficiency in oxidative phosphorylation. Cases have recently been reported in which fatal liver failure with neonatal onset was the major clinical and biochemical syndrome. In this series we reviewed the liver histology of 10 such patients who died in the first weeks of life (from 3 days to 6 mo). In six cases the diagnosis was confirmed by study of the mitochondrial respiratory chain in the muscle, liver or both; in the other four, appropriate tests were not available for diagnosis but symptoms were identical and all other diagnoses were ruled out. In all 10 cases we noted significant steatosis, mostly microvesicular; widespread hepatocytic, canalicular and bile duct cholestasis with bile thrombi and cholangiolar proliferation; and different degrees of hepatosiderosis and glycogen depletion. Fibrosis took varying forms: perisinusoidal, periportal with the formation of septa, even precirrhosis. In the two cases of infants who died, one at 5 and one 6 mo, micronodular cirrhosis was also present. Mitochondria, either densely or loosely packed, were abnormal-pleiomorphic with few or no cristae and a granular fluffy matrix. Dense, large granules were seen in two cases. The association of neonatal liver failure and hyperlactacidemia should lead to immediate examination of the respiratory chain. The expression of this mitochondrial cytopathy can be lethal, associated with severe liver damage due to the deficiency in oxidative phosphorylation.     

Testing for carotid atherosclerosis

BACKGROUND: Optometrists frequently examine patients with the signs and symptoms of carotid artery disease. Referral for appropriate testing is mandatory in such patients. METHODS: A review of the noninvasive tests which an optometrist can perform in the office is presented. The paper also describes the noninvasive tests which are performed in vascular clinics on patients in whom carotid atherosclerosis is to be ruled out. Arteriography, both conventional and digital subtraction studies, is also described. RESULTS: A discussion of the appropriate medical and surgical treatment of patients with carotid atherosclerosis and the ocular manifestations of it is included in the paper. CONCLUSIONS: With the increasing expansion of the scope of practice for optometrists, it is imperative that the signs and symptoms of carotid atherosclerosis be understood and managed appropriately. Preliminary tests for carotid arterial disease can be performed in the office, and referral for more extensive testing is better accomplished when those tests are understood by the referring optometrist.     

Hepatic amebiasis: an unusual clinical presentation

BACKGROUND: Painful liver enlargement with fever are common signs of hepatic ambiasis. Exceptionally, atypical signs may also occur including symptoms suggesting renal sepsis. CASE REPORT: An 18-year-old woman from the New Caledonia was hospitalized in metropolitan France for suspected right-sided acute pyelonephritis. Urinalysis was normal and the kidney ultrasound suggested the need for an abdominal CT-scan which evidenced a voluminous 10-cm abscess pus. Serology for amebia was positive, confirming the diagnosis of hepatic amebic abscess. Outcome was rapidly favorable with intravenous anti-parasite treatment amebic abscess. Outcome was rapidly favorable with intravenous anti-parasite treatment and percutaneous drainage. DISCUSSION: Atypical signs of hepatic ambiasis may mislead diagnosis. The absence of a fetid odor at puncture helps guide diagnosis, confirmed by serology. Percutaneous drainage can hbe proposed for voluminous abscesses or if the risk of extrahepatic complications is eminent.     

Venocclusive disease of the liver after bone marrow transplantation: the role of hemostasis

Venocclusive disease of the liver is a relatively frequent early complication of bone marrow transplantation related to pre-transplant toxic injury to the liver. Events that lead to toxicity of the liver in the pre-transplant setting are infection, anti-neoplastic and anti-infectious drug administration and radiation. The histological correlates of venocclusive disease are lesions mainly localized to structures in zone 3 of the liver acinus and in the sublobular central venules. At some point in the pathogenesis of venocclusive disease, blood clotting and inflammation occur. The first is characterized by laboratory signs of coagulation activation, by an increase in several procoagulant proteins and by a decrease in naturally occurring anticoagulants, particularly protein C, the latter being a sensitive index of liver injury. Inflammation is mediated by cytokine production, which maintains procoagulant endothelial responses and liver injury. Severe venocclusive disease is associated with multi-organ failure and elevated mortality. Attempts at finding predictive markers of the disease have succeeded in identifying some coagulation and inflammatory proteins which can be useful in predicting the occurrence of VOD in selected patient groups. The role of hemostasis in venocclusive disease is underscored also by the reports on the successful prophylaxis and management of the disease with heparin and thrombolytic agents.     

Subacute necrotizing encephalomyelopathy (Leigh's disease): a clinicopathologic study of ten cases

Archival material and clinical data of 10 autopsy cases of Leigh's disease (LS), aged from 44 days to 9 years at death, were reviewed. Development delay, irregular respiration, feeding difficulty, and abnormal eye signs were the most common symptoms. Seizures (five of ten cases) were also frequent. In most patients, the diagnosis of LS was established postmortemly by the presence of symmetrical spongiform lesions affecting several brain centers at autopsy. The histologic examination disclosed associated hypertrophic cardiomyopathy in six cases, while fatty infiltration of the hepatocytes was observed in four cases. Microvesicular degeneration of the renal tubular epithelial cells was also seen in four cases. Our observations suggest that liver and kidney involvement is a component of LS and that this rare entity has to be considered as a polysystematic disorder, able to affect other organs besides the nervous system and the heart, a fact which has not been emphasized enough in the existing literature.     

New gene assignments using a complete, characterized sheep-hamster somatic cell hybrid panel

OBJECTIVE: To assess the ability of the International Association for the Study of Pain Complex Regional Pain Syndrome (CRPS) diagnostic criteria and associated features to discriminate between CRPS patients and patients with painful diabetic neuropathy. DESIGN: Prospective assessment of signs and symptoms in a series of CRPS and diabetic neuropathy patients. SETTING: University of Washington Multidisciplinary Pain Center. PATIENTS: A consecutive series of 18 CRPS patients and 30 diabetic neuropathy patients. INTERVENTIONS: Patients completed a 10-item patient history questionnaire assessing symptoms of CRPS prior to medical evaluation. The evaluating physician completed a 10-item patient examination questionnaire assessing objective signs of CRPS. OUTCOME MEASURES: The analyses conducted were designed to test the ability of CRPS signs and symptoms and associated features to discriminate between CRPS patients and diabetic neuropathy patients. RESULTS: Data analysis suggested that CRPS decision rules may lead to overdiagnosis of the disorder. Diagnosis based on self-reported symptoms can be diagnostically useful in some circumstances. The addition of trophic tissue changes, range of motion changes, and "burning" quality of pain did not improve diagnostic accuracy, but the addition of motor neglect signs did. Test of a CRPS scoring system resulted in improved accuracy relative to current criteria and decision rules. CONCLUSIONS: Poorly understood disorders lacking prototypical signs/symptoms and diagnostic laboratory testing must rely on the development of reliable diagnostic guidelines. The results of this study should assist in the further refinement of the CRPS diagnostic criteria.     

Co60 gamma-ray sensitivity of a series of strains of Saccharomyces cerevisiae yeasts bearing different mutations. I. Radiosensitivity of haploid strains

Sensitivity to gamma-rays Co60 of haploid strains of Saccharomyces cerevisiae carrying ade1-6 mutations and dominant, semidoninant and recessive suppressors was investigated. It was shown that 3 out of 4 studied strains with ade1-6 mutation had reliable increased radioresistance. The increased radioresistance was observed also in strains carrying, beside ade1-6 mutation, dominant and semidominant suppressors. However the strain carrying a recessive suppressive mutation turned to be radiosensitive. A conclusion is drawn that rediosensitivity of yeast cells can be influenced by different mutations affecting the process of cell metabolism.     

The validity of a nursing assessment and monitoring of signs and symptoms scale in ICU and non-ICU patients

PURPOSE: This study examined the validity of medical-record-based nursing assessment and monitoring of signs and symptoms (nursing surveillance) in predicting patients who were admitted to ICUs and those admitted to non-ICUs. The association of this assessment and monitoring with differences in an intermediate patient outcome, instability at discharge, was also explored. Patients admitted to either setting with a diagnosis of acute myocardial infarction, cerebrovascular accident, congestive heart failure, or pneumonia, were included in the study. METHOD: A secondary analysis was carried out using a subset of data originally collected for a quality-of-care study. Data from the medical records of 11,246 patients (52% female, 48% male) with a mean age of 76.4 years were used in the present study. RESULTS: ICU patients (n = 3969) were found to have a longer length of stay and to be sicker on admission than non-ICU patients (n = 7277). Overall, patients in the ICU received significantly higher nursing assessment and monitoring of signs and symptoms scores than non-ICU patients. Nursing assessment and monitoring of signs and symptoms scores were lower for patients discharged with greater instability for three of the four diseases (cerebrovascular accidents, congestive heart failure, and pneumonia).     

Retained austenite and mechanical properties in bainite transformed low alloy steels

Uniform ductility and formability of low alloy steels can be improved by the transformation plasticity effect of metastable retained austenite. In this work, intercritical annealing followed by bainite transformation resulted in the retention of austenite with sufficient stability for transformation plasticity interactions. The effect of retained austenite on mechanical properties was studied in two low-alloy steels. Bainite transformation was carried out in the range of 400 to 500°C. The strength properties (yield strength and ultimate tensile strength) were more sensitive to bainite isothermal transformation temperature than holding time. Maximum strength properties were obtained for the lower transformation temperatures. On the other hand, high uniform and total elongation values were obtained at lower transformation temperatures but were sensitive to bainite isothermal transformation time. Variations in uniform elongation with holding time were linked to variations in retained austenite stability. Maximum values of uniform elongation occurred at the same holding times as the maximum amount of retained austenite. The same was true for total elongation and ultimate tensile strength. The above results indicate a strong correlation between retained austenite stability and uniform ductility and suggest that further optimisation regarding chemical composition and processing with respect to austenite stabilisation may lead to a new class of triple-phase high-strength high-formability low-alloy steels.     

Lead suppresses chimeric human transferrin gene expression in transgenic mouse liver

The major iron-transport protein in serum is transferrin (TF) which also has the capacity to transport other metals. This report presents evidence that synthesis of human TF can be regulated by the metal lead. Transgenic mice carrying chimeric human TF-chloramphenicol acetyl transferase (CAT) genes received lead or sodium salts by intraperitoneal injections or in drinking water. Transgene expression in liver was suppressed 31 to 50% by the lead treatment. Lead regulates human TF transgenes at the mRNA level since liver CAT enzyme activity, CAT protein, and TF-CAT mRNA levels were all suppressed. The dosages of lead did not alter synthesis of the other liver proteins, mouse TF and albumin, as measured by Northern blot analysis of total liver RNA and rocket immunoelectrophoresis of mouse sera. Moderate levels of lead exposure were sufficient to evoke the human TF transgene response; blood lead levels in mice that received lead acetate in drinking water ranged from 30 micrograms/dl to 56 micrograms/dl. In addition to suppressing expression of TF-CAT genes in transgenic mice, lead also suppressed synthesis of TF protein in cultured human hepatoma HepG2 cells. The regulation of human TF apparently differs from the regulation of mouse TF which is unresponsive to lead exposure.     

Urinary non-precipitable lead in lead workers

Sixty-six workers engaged in lead-glazing pottery with a presumed moderate exposure to lead were studied. The group comprised 20 men with long-term exposure to lead and positive laboratory signs of increased lead absorption (Group A); 22 with long-term exposure and negative laboratory signs (Group B); 11 with short-term exposure and positive laboratory signs (Group C); and 13 with short-term exposure and negative laboratory signs (Group D). In addition, 14 workers employed in casting the kelmet alloys with presumed heavy exposure to lead (Group E) and seven healthy individuals (Group F) were included. Urine samples from all the subjects were analysed to determine, first, the total lead using the ashing technique, and then the precipitable lead using the coprecipitation technique of Cholak, Hubbard, and Burkey (1948), but modified slightly by us. Thus, the non-precipitable lead fraction in urine was the difference between the two measurements and this was also expressed as a percentage of the total lead. The mean total lead and the mean proportion of non-precipitable lead were 0.62 mumol/l and 48.7%, 0.35 mumol/l and 44.9%, 0.40 mumol/l and 48.9%, 0.17 mumol/l and 24.6%, 1.43 mumol/l and 44.3%, 0.14 mumol/l and 18.8% for Groups A, B, C, D, E, and F respectively, showing that a large part of urinary lead was eliminated as precipitable lead in Groups D and F who had normal lead excretion, while about half was eliminated as non-precipitable lead in the other four groups who had excessive lead excretion. No essential difference in the proportion of non-precipitable lead among Groups A, B and C excluded the possibility that the proportion might be directly related to the period of exposure to lead and to the laboratory findings of excessive lead absorption. The mean proportion of non-precipitable lead for the physiological (up to 0.240 mumol/l), intermediate (0.241 to 0.721 mumol/l), and excessive (above 0.722 mumol/l) total lead levels was 26.7, 41.3, and 52.3% respectively, in the lead workers comprising Groups A, B, C, and E each showing increased lead excretion when grouped together. these data suggested that, when urinary lead is within the normal range, it is excreted largely as precipitable lead even in individuals exposed to lead, and that the principal conditions determining the excretion of non-precipitable lead would be the current or recent degree of lead absorption. The excretory mechanisms and the biological significance of the non-precipitable lead are also discussed.     

Retropharyngeal abscess after blunt trauma in an adolescent

Retropharyngeal abscess is an unusual infection in teenagers, and it is rarely associated with blunt trauma. We present the case of 17-year-old male who developed signs and symptoms of retropharyngeal abscess soon after being struck by a car. The case illustrates that retropharyngeal abscess should be considered, even in an adolescent, if the patient has fever, neck stiffness, and sore throat with symptoms out of proportion to the oropharyngeal findings.     

Lead poisoning in a dog

A case of lead poisoning caused by ingestion of a lead roof-washer is described in a one-year-old, spayed Fox Terrier bitch, presented with nervous signs, and basophilic stippling of red blood cells. Blood concentrations of lead were in the low toxic range. Radiography of the abdomen revealed radio-dense objects in the stomach, which on gastrotomy included a lead roof-washer. Prior to removal of the foreign bodies, the dog showed remarkable improvement on non-specific symptomatic treatment alone, and recovered well after surgery, only to die unexpectedly several hours later. Concentrations of lead in the liver and kidneys were extremely high, and histology revealed typical intracellular inclusions and organ degeneration. In the light of these findings, it is suggested that all cases of suspected or confirmed lead poisoning be given specific chelation therapy.