Treatment of chronic hepatitis C: Improved combination therapy

There has been considerable progress in the treatment of chronic hepatitis C since the first report that interferon (IFN) monotherapy was effective in 1989. Early results were meager, with sustained loss of hepatitis C virus from blood in fewer than 10% of cases. The combination of IFN with the oral nucleoside analogue ribavirin was a major breakthrough in clinical hepatology; it led to dramatic increases in treatment responses, with 30% to 40% of patients clearing virus. Pegylated IFNs that have prolonged activity and can be dosed once a week have now replaced standard IFNs. The combination of pegylated IFN with ribavirin is the new standard of care; it causes sustained loss of virus in more than half of treated patients. Treatment responses continue to be highly dependent on viral genotype. Patients with genotype 1, the most common type in the United States, have a sustained clearance rate of 42% to 46%, whereas those with genotype 2 or 3 have a response rate approaching 80%.     

Aluminum-citrate interaction in end-stage renal disease.

The influence of a sodium citrate/citric acid mixture on the gastrointestinal (GI) absorption of aluminum (Al) from an Al(OH)3 preparation was evaluated in six stable maintenance hemodialysis patients. Plasma Al concentrations were determined serially after each of the following treatment sequences (I) Al(OH)3; (II) Al(OH)3 + sodium citrate/citric acid; (III) sodium citrate/citric acid; (IV) Al(OH)3 + NaHCO3. AUC0-8 for plasma Al from 0 to 8 hours was significantly greater (p less than 0.05) for Al(OH)3 + sodium citrate/citric acid (73 +/- 23 micrograms.hr/l; mean +/- SEM) than Al(OH)3 (16 +/- 30 micrograms.hr/l); sodium citrate/citric acid (-27 +/- 14 micrograms.hr/l); or Al(OH)3 + NaHCO3 (6 +/- 22 micrograms.hr/l). The 24 hour Al level remained above baseline (p less than 0.03) following Al(OH)3 + sodium citrate/citric acid (31 +/- 12 (pre) vs 54 +/- 14 micrograms/l (post), in contradistinction to study limb: l (34 +/- 14 vs 30 +/- 12 micrograms/l); III (79 +/- 40 vs 65 +/- 35 micrograms/l); and IV (71 +/- 37 vs 66 +/- 42 micrograms/l). We conclude that the GI absorption of Al from Al(OH)3 is enhanced by citrate in patients undergoing hemodialysis and that elevations of plasma Al persist longer. The concomitant administration of citrate and Al-containing phosphate (PO4) binders should be avoided in patients with end-stage renal disease (ESRD). NaHCO3 may serve as an alternative therapy for metabolic acidosis with less risk of enhancing Al absorption.     

Recommendations for the management of low risk obstetric patients.

Specific interventional procedures have enjoyed widespread popularity in the United States in the routine management of low risk obstetric patients without the benefit of clinical studies attesting to their utility. A review of the literature was conducted to survey obstetric practice with regard to amniotomy, intravenous fluids, third stage administration of oxytocics, episiotomy and continuous fetal monitoring.     

An evaluation of provider-related and disease-related morbidity in a level I university trauma service: directions for quality improvement.

As the number of preventable trauma-related deaths plateaus as a result of trauma system development, new directions for quality improvement in trauma care must come from analyzing morbidity with standardized methods to establish thresholds for provider-related and disease-specific complications. To establish such thresholds and determine priorities for improvements in quality all trauma patients who died, who were admitted to the ICU or OR, who were hospitalized for more than 3 days, or who were interfacility transfers to an academic trauma service, were concurrently evaluated for 1 year. All complication events were defined, reviewed, tabulated, and classified using 135 categories of complications. These categories were subdivided into provider-specific and disease-specific complications. Provider-related complications were classified as justified or unjustified to allow identification of events with a potential for improvement. A total of 1108 patients were admitted (mean ISS, 17); there were 97 deaths. Three potentially preventable deaths were identified, 857 complication events were identified, and 285 provider-related complications were responsible for errors with potential for improvement in 59 events (21%). Disease-specific morbidity was primarily related to infection; pneumonia accounted for 36% of all infectious complications and systemic infection for only 8.6% of infectious complications. Organ failure and other major systemic complications occurred in 2%-8% of patients. This type of analysis forms the basis on which to determine thresholds of provider-specific and disease-specific morbidity in a trauma hospital and serves as a guide to direct efforts toward continuous quality improvement.     

Methylmercury poisoning: Long-term clinical,radiological, toxicological,and pathological studies of an affected family

For 3 months in 1969 a family in the United States that included a pregnant mother consumed pork containing methylmercury. Children, aged 20, 13, and 8 years and a neonate, developed severe neurological signs. Twenty-two years later, the 2 oldest had cortical blindness or constricted visual fields, diminished hand proprioception, choreoathetosis, and atentional deficits. Magnetic resonance images showed tissue loss in the calcarine and parietal cortices and cerebellar folia. The youngest had quadriplegia, blindness, and severe mental retradation until their deaths. The brain of the 8-year-old who died at age 30 showed cortical atrophy, neuronal loss, and gliosis, most pronounced in the paracentral and parietooccipital regions. The total mercury level in formalin-fixed, left occipital cortex was 1,974 ng/gm as measured by atomic absorption. Regional brain mercury levels correlated with extent of brain damage. A control patient had 38.5 ng of mercury/gm in the occipital cortex. Systemic organs in the patient and a control subject had comparable mercury levels. In mercury-intoxicated rats, we found that only 5 to 10% of total brain mercury was lost by formalin fixation. Brain inorganic mercury in the patient ranged from 82 to 100%. Since inorganic mercury crosses the blood-brain barrier poorly, biotransformation of methyl to inorganic mercury may have occurred after methylmercury crossed the blood-brain barrier, accounting for its persistence in brain and causing part of the brain damage.     

Role of frozen section and clinical parameters in distinguishing benign from malignant follicular neoplasms of the thyroid.

The determination of malignancy preoperatively or intraoperatively is difficult in patients with follicular neoplasms of the thyroid. This study reviews a series of 395 patients treated for follicular neoplasms at the Vancouver General Hospital and the British Columbia Cancer Agency between the years of 1955 and 1988, 198 of whom had frozen section at the time of surgery. Frozen section was 79% accurate in differentiating follicular adenomas from carcinomas, with a sensitivity of 52% and a specificity of 100%. The positive predictive value of a frozen section showing carcinoma was 100%, and the negative predictive value was 73%. An incorrect diagnosis of a benign lesion was made in 21% of patients in whom the final diagnosis by fixed section was carcinoma. These same statistics were calculated for patients aged greater than 50 years, tumor size greater than 3 cm, and patients with a history of previous neck irradiation, three clinical factors shown in a previous study to be strong prognostic indicators of malignancy. The results were compared with those found by frozen section. The implications of these results in terms of patient management are discussed.     

Platelet phospholipid synthesis in Alzheimer's disease

The rates of incorporation of [3H]choline and [3H]ethanolamine into membrane phospholipids of platelets from 22 drug-free Alzheimer's disease patients and 18 normal elderly controls were compared. No significant differences between groups were found. If alterations in lipid metabolism are involved in the pathophysiological processes underlying Alzheimer's disease, such alterations are not manifest in measures of radiolabeled base incorporation into platelet phospholipids.