Dihydrocodeine--drug of use or misuse?
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Analgesics, Opioid↗
Biomedical subjects
M Black
Publications and source records attributed to M Black.
Hydrazine, cancer, the Internet, isoniazid, and the liver.
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Antineoplastic Agents↗
Granulomatous Liver Disease.
In the United States, the majority of patients with granulomatous liver disease do not have an identifiable cause. When a specific diagnosis can be made, therapy should be directed at eradicating the cause. A plan of management must recognize the drug history and nationality of the patient, chest radiograph, slit lamp examination of the eyes, skin tests, special stains of liver biopsies, and serum antibodies. In those patients for whom a specific diagnosis cannot be established, the use of corticosteroids requires that the patient have a clinical justification for treatment or manifest important changes in findings of liver biopsies. Patients selected for steroid treatment should be subjected to close laboratory monitoring, and the decision to continue therapy should be based on objective parameters. Treatment of steroid-resistant disease might require methotrexate, chloroquine, cyclosporine, azathioprine, or ursodeoxycholic acid.
Journal Article↗
Extracardiac conduit fontan procedure: early and intermediate results.
OBJECTIVE: The extracardiac Fontan procedure, as compared with classic atriopulmonary connections, may have the potential for optimizing ventricular and pulmonary vascular function by maximizing the laminar flow principle, by the avoidance of intra-atrial suture lines and cardiac manipulation, and by minimizing cardiopulmonary bypass time. In this study the clinical results of this procedure are assessed. METHODS: From January 1990 until January 1997, 45 patients (33 males and 12 females) with a median age of 4.0 years (range 2.7-38 years) underwent an extracardiac Fontan procedure for univentricular physiology. The underlying diagnoses included tricuspid atresia (n=19), double-inlet left ventricle (n=11), and complex anomalies (n=15). Forty patients (89%) were in sinus rhythm. The median ventricular ejection fraction was 60%. In 37 patients (82%) the procedure was staged. RESULTS: Median cardiopulmonary bypass time was 72 min, with a decrease to a median time of 24 min in the last ten patients. Aortic cross-clamping was avoided in 33 patients (73%). The intraoperative Fontan pressure and transpulmonary gradient were low: 13.6+/-3.2 and 8.5+/-3.9 mmHg, respectively. Transient supraventricular tachyarrhythmias were observed in six patients (13%). There was no early or late mortality. At a median follow-up of 64 months (range 26-105 months), 39 patients (87%) were in NYHA class I, four (9%) were in NYHA class II, and two (4%) were in class III. Forty patients (89%) remained in sinus rhythm. The median ventricular ejection fraction was 59%. The median arterial oxygen saturation raised from 82% preoperatively to 97%. Functional class (P=0.02), maintenance of sinus rhythm (P=0.04), and preservation of ventricular function (P=0.05) was superior in patients who were appropriately staged. None of the patients had atrial thrombus, chronic pleural effusions, or protein losing enteropathy. CONCLUSIONS: In the majority of patients, the extracardiac Fontan procedure, when performed as a staged procedure, provides excellent early and midterm results in terms of quality of life, maintenance of sinus rhythm, and preservation of ventricular function.
Adolescent↗
Alpha1-antichymotrypsin globules within hepatocytes in patients with chronic hepatitis C and cirrhosis.
Alpha1-antichymotrypsin (A1AC) is an acute phase serine protease inhibitor, similar to alpha1-antitrypsin (A1AT) in amino acid sequence. A1AT deficiency is known to be associated with emphysema and cirrhosis; deficiency of serum A1AC has been reported to be associated with emphysema, childhood asthma, and cryptogenic cirrhosis. The hepatocyte globules associated with A1AT deficiency have been well described; A1AC deficiency also has been reported to be associated with hepatocyte globules. The aim of this study was to describe the globules of A1AC and to compare them with A1AT globules. Immunohistochemistry for A1AC and A1AT was performed on liver biopsy specimens from 15 hepatitis C virus (HCV)-positive cirrhotic patients, 14 non-HCV cirrhotic patients, and 12 other patients with chronic hepatitis C but no cirrhosis, all of whom had known serum levels of A1AC; most had known serum levels of A1AT. Five of 15 HCV-positive cirrhotic patients, 1 of 14 non-HCV cirrhotic patients, and 1 of 12 noncirrhotic chronic hepatitis C patients had A1AC globules. Two of 15 HCV-positive cirrhotic patients and 2 of 14 non-HCV cirrhotic patients had A1AT globules. Histologically, the globules of A1AC were similar to those of A1AT but were smaller and fewer; the PAS/D stain was not as helpful for A1AC as it was for A1AT; immunohistochemistry was most useful. There was not a good correlation between serum levels of A1AC and its globules in hepatocytes. A1AC globules should be included in the differential diagnosis of hepatocyte inclusions.
Adult↗
Drug related deaths amongst Glasgow city hostel dwellers.
The problems of homelessness and drug misuse are every day issues encountered in today's society. Over the past 2 years the number of hostel residents overdosing within their rooms in the city of Glasgow was shown to increase. Approximately three-quarters of deaths involved heroin, of which 56% also involved at least one benzodiazepine. This paper demonstrates a dearth in the literature relating to drug misuse amongst the homeless population, highlighting an area in need of address by the appropriate authorities.
Journal Article↗
Three-dimensional esophageal varix model quantification of variceal volume by high-resolution endoluminal US.
BACKGROUND: The purpose of this study was to evaluate the accuracy and reproducibility of three-dimensional volume measurements by high-resolution endoluminal ultrasound in an esophageal varix model. METHODS: An esophageal varix model was made by filling three esophageal dilatation catheters with various volumes of water. A 20 MHz ultrasonography transducer was then pulled along the length of the catheters at a constant rate (1.25 mm/sec) while videotaping the procedure. Cross-sectional surface area measurements of each catheter were taken every second and the cross-sectional surface area was multiplied by the length of each catheter, as determined by high-resolution endoluminal ultrasound, to determine the volume in each catheter. Interobserver variability was calculated, and three-dimensional reconstruction was performed. RESULTS: The measured volumes corresponded closely with the actual volumes with an error ranging from 0% to 15.4%. The correlation between actual and measured volumes was r = 0.988. The interobserver variability ranged from r = 0.951 to r = 0.994. Actual esophageal varices were then imaged in a similar fashion to determine the feasibility of this method in patients with esophageal varices. CONCLUSIONS: High-resolution endoluminal ultrasound is an accurate and reproducible method of measuring volumes in an esophageal varix model and can be used in a clinical setting to determine variceal volume. Volume studies are now underway in human subjects.
Endosonography↗
Cerebral hyperthermia in children after cardiopulmonary bypass.
BACKGROUND: Cerebral hyperthermia after hypothermic cardiopulmonary bypass has been poorly documented for adults and never in children. This study was designed to monitor brain temperature during and up to 6 h after cardiopulmonary bypass in infants and children. METHODS: Fifteen infants and children, between 3 months and 6 yr of age, were studied. A right retrograde jugular bulb catheter was used to measure the jugular venous bulb temperature (JVBT) during the procedure and the first 6 h in the critical care unit. The temperature of the blood from the bypass machine was measured at the aorta through the cannula using an indwelling temperature probe. All data were acquired every minute. RESULTS: The age of the patients ranged from 3 to 71 months (median, 15 months). The mean weight was 11.5 +/- 8.4 kg. The mean JVBT recorded at the end of cardiopulmonary bypass was 36.9 +/- 1.4 degrees C but reached 39.6 +/- 0.8 degrees C after six h (P < 0.01). The kinetics of brain rewarming was determined by the slope of the mean JVBT and corresponded to y +/- 0.006x + 37.21 (r2 = 0.97). The JVBT differed from the tympanic temperature after 200 min (P < 0.01) and the lower esophageal (P < 0.05) and rectal (P < 0.001) temperatures after 300 min. After 6 h, the tympanic, rectal, and lower esophageal temperatures were 37.8 +/- 0.9, 37.7 +/- 0.6, and 38.4 +/- 0.7 degrees C, respectively, whereas the JVBT was 39.6 +/- 0.8 degrees C (P < 0.001). However, the correlation coefficients between the JVBT and the tympanic, rectal, and esophageal temperatures were 0.98, 0. 85, and 0.97, respectively. No complications were recorded with placement of the jugular bulb catheter. CONCLUSIONS: Mean JVBT was significantly increased over the mean core temperature at all times from rewarming by cardiopulmonary bypass onward. Although the lower esophageal, rectal, and tympanic temperatures correlated well with JVBT, all three failed to reflect JVBT during recovery. This observation might help to elucidate factors involved in the functional and structural neurologic injury known to occur in pediatric patients.
Body Temperature↗
Public health: just processes?
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Community Participation↗
Correlation between increased colloid osmotic pressure and the resolution of refractory ascites after transjugular intrahepatic portosystemic shunt.
BACKGROUND: This study compared the changes in serum albumin, globulin, and colloid osmotic pressure (COP) before and after transjugular intrahepatic portosystemic shunt (TIPS) or large volume paracentesis (LVP) in patients with ascites. METHODS: Of 23 patients with refractory ascites, 17 had TIPS and 6 had LVP with infusion of albumin. Colloid osmotic pressure measurements were calculated, using the formula previously proposed by Hoefs: COP = A (1.058G + 0.163A + 3.11) where A = serum albumin and G = serum globulin. RESULTS: After 1 month, ascites resolved in 9 of the 17 patients who had TIPS and in none of the 6 who had LVP. Colloid osmotic pressure increased significantly in patients whose ascites resolved after TIPS. Colloid osmotic pressure did not change in the patients whose ascites did not resolve after TIPS, and COP decreased significantly in the LVP group. A statistically significant difference was found in the pre-TIPS COP measurements between those patients who had resolution of ascites and those who did not. A pre-TIPS COP of < or =20 mm Hg predicted resolution of ascites with an 88% sensitivity and a 78% specificity. CONCLUSIONS: Serum COP increased significantly in patients with resolution of ascites but remained unchanged in patients with persistent ascites after TIPS. Serum COP decreased after LVP. A statistically significant difference in the pre-TIPS COP was found between patients whose ascites resolved and patients having persistent ascites.
Adult↗
Drug-related deaths among recently released prisoners in the Strathclyde Region of Scotland.
Drug abuse and its consequences are everyday problems encountered globally, and Scotland is no exception. During a study of drug-related deaths in the Strathclyde region of Scotland it was noted that known drug users who had recently been released from prison were at high risk of dying from a drug overdose. The majority of deaths occurred within one week of the release date and polydrug use was prevalent. Morphine was the most frequently encountered drug and this was found in combination with benzodiazepines in a significant number of cases. This paper highlights the dangers of resuming drug consumption following a period of abstinence.
Adult↗
Employers' liability & first aid.
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Equipment and Supplies↗
Repeat exposure to incremental doses of acetaminophen provides protection against acetaminophen-induced lethality in mice: an explanation for high acetaminophen dosage in humans without hepatic injury.
In studies designed to simulate a clinical observation in which an individual became tolerant to normally lethal doses of acetaminophen (APAP), mice were pretreated with increasing doses of APAP for 8 days and challenged on day 9 with normally supralethal doses of APAP. These animals developed minimal hepatotoxicity after a challenge dose with a fourfold increase in LD50 to 1,350 mg/kg. The pretreatment regimen resulted in hepatic changes including: centrilobular localization of 3-(cysteine-S-yl)APAP protein adducts, selective down-regulation of cytochrome P4502E1 (CYP2E1) and CYP1A2 that produced the toxic metabolite, N-acetyl-p-benzoquinone imine, higher levels of reduced glutathione (GSH), centrilobular inflammation, and a fourfold increase in hepatocellular proliferation. The protection against the lethal APAP doses afforded by pretreatment is secondary to these changes and to the associated regional shift in the bioactivation of the APAP challenge dose from centrilobular to periportal regions where CYP2E1 is not found, protective GSH is more abundant, and where cell-proliferative responses are better able to sustain repair. This shift in APAP bioactivation results in less-intense covalent binding that is more diffuse and spread uniformly throughout the hepatic lobe, most likely contributing to protection by delaying the early onset of liver injury that has been generally associated with centrilobular localization of the adducts. Intervention of APAP pretreatment-induced cell division in mice with colchicine left them resistant to a 500-mg/kg (normally lethal) dose of APAP, but unable to survive a 1,000-mg/kg APAP challenge dose. The data demonstrate multiple mechanistic components to the protection afforded by APAP pretreatment. Whereas metabolic and physiological changes not dependent on cell proliferation are adequate to protect against 500 mg/kg APAP, these changes plus a potentiated cell-proliferative response are necessary for protection against the supralethal 1,000-mg/kg APAP dose. Furthermore, the data document an uncoupling of the traditional association between covalent binding and toxicity, and suggest that the assessment of toxicity following repeated or chronic APAP exposure must consider altered drug interactions and parameters besides those historically used to assess acute APAP overdose.
Acetaminophen↗
High-resolution endoluminal sonography assessment of the hematocystic spots of esophageal varices.
BACKGROUND: Many variables are associated with an increased potential for esophageal variceal rupture, especially the presence of hematocystic spots and other red signs on upper endoscopy. The etiology of hematocystic spots is unknown. High-resolution endoluminal sonography has been shown to be an accurate and sensitive imaging modality for detection, as well as the qualitative and quantitative assessment of esophageal varices. Because the high-resolution endoluminal sonography transducer permits detailed resolution of submucosal structures thereby allowing more precise examination of the actual wall of the varix, we sought to image variceal hematocystic spots in an effort to better define their anatomy. METHODS: Simultaneous upper endoscopy and high-resolution endoluminal sonography were performed in 68 patients with cirrhosis. Endoscopy was performed as part of screening for varices during evaluation for liver transplantation or in patients with previous presumed variceal bleeding. On endoscopy and high-resolution endoluminal sonography, two independent reviewers identified the same 10 patients having esophageal varices with hematocystic spots. The patients who had bled from their varices had not received prior endoscopic treatment. RESULTS: Hematocystic spots as seen with high-resolution endoluminal sonography imaging appeared as saccular aneurysm like projections on the variceal surface in 6 of 10 patients. Four of six patients would later have recurrent bleeding; two of these patients were again noted to have hematocystic spots on endoscopy with a similar corresponding high-resolution endoluminal sonography appearance. Patients without hematocystic spots did not have similar high-resolution endoluminal sonography imaging. CONCLUSION: Aneurysm-like projections in the wall of varices may represent focal weaknesses of the variceal wall and thus play a role in the pathophysiology of esophageal variceal rupture. The present findings may help to explain why there is an increased risk of variceal hemorrhage associated with the presence of hematocystic spots on esophageal varices.
Endoscopy, Digestive System↗
Calculation of esophageal variceal wall tension by direct sonographic and manometric measurements.
BACKGROUND: LaPlace's law determines the wall tension of a tubular system by measuring the radius (r), wall thickness (w), and pressure gradient of a tubular structure: wall tension = pressure gradient x r/w. In theory, the determination of wall tension could provide the most accurate method of predicting the likelihood of esophageal variceal rupture. Using high-resolution endoluminal sonography, we measured the variceal wall thickness and radius. Using direct needle puncture, we measured the intravariceal pressure in three patients. We then calculated the wall tension by the LaPlace equation for each of seven varices. METHODS: A 20 MHz ultrasonographic transducer was used to image esophageal varices. Outer and inner variceal wall circumferences were measured at a cross section of each varix. The radius and wall thickness of each varix were then calculated. Pressure measurements were obtained in the esophageal lumen and variceal lumen by direct needle puncture of the varices. The pressure gradient was then calculated (esophageal lumen - variceal lumen). RESULTS: The wall tension of the varices from three patients was determined. There was a linear relation (r = 0.88) between the wall tension and pressure gradient. CONCLUSIONS: This is a novel technique by which esophageal variceal wall tension can be directly measured. Such information may be useful in the future treatment of patients with portal hypertension by which risk stratification may be determined and pharmacologic response to therapy may be measured.
Blood Pressure↗
Massive hemoptysis secondary to bronchial collaterals: treatment with use of TIPS and embolization.
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Adult↗
Water content, raffinose, and dehydrins in the induction of desiccation tolerance in immature wheat embryos
Desiccation tolerance is initiated in wheat (Triticum aestivum L.) embryos in planta at 22 to 24 d after anthesis, at the time that the embryo water content has decreased from about 73% fresh weight (2.7 g water/g dry weight) to about 65% fresh weight (1.8 g water/g dry weight). To determine if desiccation tolerance is fully induced by the loss of a relatively small amount of water, detached wheat grains were treated to reduce the embryo water content by just a small amount to approximately 69% (2.2 g water/g dry weight). After 24 h of such incipient water loss, subsequently excised embryos were able to withstand severe desiccation, whereas those embryos that had not previously lost water could not. Therefore, a relatively small decrease in water content for only 24 h acts as the signal for the development of desiccation tolerance. Embryos that were induced into tolerance by a 24-h water loss had no detectable raffinose. The oligosaccharide accumulated at later times even in embryos of detached grains that had not become desiccation tolerant, although tolerant embryos (i.e. those that previously had lost some water) contained larger amounts of the carbohydrate. It is concluded that desiccation tolerance and the occurrence of raffinose are not correlated. Immunodetected dehydrins accumulated in embryos in planta as desiccation tolerance developed. Detachment of grains induced the appearance of dehydrins at an earlier age, even in embryos that had not been made desiccation tolerant by incipient drying. It is concluded that a small reduction in water content induces desiccation tolerance by initiating changes in which dehydrins might participate but not by their interaction with raffinose.
Journal Article↗
Biochemical and viral response to consensus interferon (CIFN) therapy in chronic hepatitis C patients: effect of baseline viral concentration. Consensus Interferon Study Group.
OBJECTIVE: The effect of baseline viral concentration on response was assessed as part of a multicenter phase 3 trial evaluating the safety and efficacy of CIFN therapy for chronic HCV infection. METHODS: Patients (n = 472) received either CIFN 9 microg or IFN alpha-2b 3 MU subcutaneously t.i.w. for 24 wk, followed by 24 wk of observation. RESULTS: Efficacy was assessed by the percentage of patients who achieved normal ALT values or undetectable HCV RNA values (using RT-PCR with a sensitivity of 100 copies/ml). There was a clear relationship between baseline viral concentration and either ALT or HCV RNA response; patients with lower titer HCV RNA had better response rates. End-of-treatment HCV RNA responses were better for patients with low viral concentrations treated with CIFN (51%) than for patients treated with IFN a-2b (31%) (p = 0.03). ALT responses in patients with low viral concentrations were 60% for CIFN-treated patients and 27% for IFN alpha-2b-treated patients (p < 0.01) at the end of treatment. Patients with high titer HCV RNA were more likely to have a sustained HCV RNA response after treatment with CIFN 9 microg, compared with those treated with IFN alpha-2b (7% vs 0%, p = 0.03). CONCLUSIONS: Both genotype and baseline viral concentration were independent factors that affected response to interferon.
Adult↗