About turn in US on interferon alfa.
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Biomedical subjects
Publications and source records attributed to J Roberts.
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While there is evidence that hepatitis C virus (HCV) does not cause fulminant non-A, non-B hepatitis, the causal agent remains unknown. To evaluate the role of hepatitis B virus (HBV) in this disease, we used a two-step polymerase chain reaction (PCR) to amplify the surface and core regions of HBV DNA in serum and liver samples taken prospectively from twenty-six patients (mean age 36 years, range 1 to 64) with acute hepatic failure undergoing liver transplantation. HBV DNA was absent from the serum of all patients before transplantation. Seventeen patients were diagnosed as having non-A, non-B hepatitis because they lacked serological evidence of hepatitis A virus or HBV infection. Liver samples were taken from twelve of these patients, and six samples were positive for HBV DNA. By contrast HBV DNA was not detected in liver from three patients with acute liver failure caused by hepatitis A or toxins. HCV RNA was not found in pretransplant samples by PCR. Four of the six patients with detectable HBV DNA in liver and presumptive non-A, non-B hepatitis had detectable HBV DNA in serum after transplantation. One additional patient who did not donate pretransplant liver had HBV DNA in a post-transplant serum sample. Thus, HBV DNA was present before or after transplantation in seven of seventeen patients with apparent non-A, non-B hepatitis. Three of five patients with detectable post-transplant serum HBV DNA were serologically positive for HBV surface antigen. These findings indicate that HBV may be a common cause of fulminant hepatic failure in patients lacking serological evidence of HBV infection.
The opening of duplex DNA in the elongation phase of transcription by Escherichia coli RNA polymerase in vivo was detected at a regulatory site where a prolonged pause in transcription occurs. Single-stranded DNA in the transcription bubble was identified by its reactivity with potassium permanganate (KMnO4). The elongation structure in vivo was similar to that of transcription complexes made in vitro with some differences. The observed reactivity to KMnO4 of the DNA template strand was consistent with the existence of an RNA-DNA hybrid of about 12 nucleotides.
The characteristic pathological features of Huntington's disease (HD) are neostriatal atrophy and neuronal loss. Although neuroradiological studies often show caudate atrophy in patients with moderate HD, frequently no caudate atrophy is found early in the illness. There have been no quantitative reports to date on in vivo putamen volume measures in mild HD, although the structure is known to be neuropathologically involved in the illness. We measured volumes of caudate nucleus and putamen and bicaudate ratios (BCR) from magnetic resonance images, blind to diagnosis, in 15 patients with mild HD and 19 age- and sex-matched control subjects using a computerized image analysis system. The region showing greatest atrophy was the putamen, which was reduced 50.1% in mean volume in HD patients compared with control subjects (p less than 0.000001). In contrast, caudate volume was reduced 27.7% (p = 0.004). BCR was increased 28.5% in HD patients (p = 0.0002). Discriminant function analysis was 94% effective in identifying the diagnostic group based on putamen volume alone, whereas caudate measures had considerable overlap. Correction of putamen volume for head size led to 100% separation by group. Putamen measures and BCR correlated with neurological examination scores but caudate volume did not. Volumetric measurement of putamen is a more sensitive indicator of brain abnormalities in mild HD than measures of caudate atrophy.
In this study we examined multiple serial liver biopsy specimens from liver transplant recipients to determine the pathological features of hepatitis C virus-induced hepatitis. Hepatitis C virus infections acquired after transplantation and previous infections that recurred in patients after transplantation were confirmed by the results of the polymerase chain reaction. Of 43 patients infected with the hepatitis C virus, 18 had a mild form of chronic hepatitis. Four patients had hepatitis that progressed to focal bridging fibrosis or cirrhosis. There were no significant clinical or pathological differences between infections acquired after transplantation and recurrent infections (as determined by polymerase chain reaction) except that acquired infections more often developed into hepatitis. Findings indicative of hepatitis C infection included portal and parenchymal mononuclear infiltrates of varying degrees, acidophilic necrosis and swollen hepatocytes. Other common findings included lymphoid aggregates, bile duct damage and fatty change. Atypical pathological conditions included extensive hepatocyte swelling or acidophilic necrosis with minimal inflammation mimicking ischemia and ductal or ductular damage and proliferation with mixed portal infiltrates mimicking rejection or obstruction. We conclude that in transplant recipients infection by the hepatitis C virus usually produces a mild disease state, but the diagnosis of hepatitis can be difficult to make because indicators of hepatitis may mimic those of rejection, ischemia, obstruction or other hepatic infections. Serial biopsy specimens with persistent pathology and polymerase chain reaction may be necessary to define the presence of a hepatitis C virus lesion.
In Japan, the presence of a large regenerative nodule within a cirrhotic liver, referred to as a macroregenerative nodule or adenomatous hyperplasia, is thought to play a role in the pathogenesis of hepatocellular carcinoma. These lesions, however, have received little attention outside of Japan. We examined 110 sequentially explanted cirrhotic livers for the presence of such nodules. By gross examination, 19 livers (17.3%) had 40 nodules (10 livers had more than one nodule) between 0.8 and 3.5 cm in diameter. By histological examination, 28 of these were macroregenerative nodules and 12 were hepatocellular carcinomas. Three of these hepatocellular carcinomas, however, appeared to have arisen in association with a macroregenerative nodule. We found that the architectural features of thickened cell plates, formation of trabeculae and loss of reticulin were usually very helpful in differentiating benign macroregenerative nodules from hepatocellular carcinoma. The incidence of macroregenerative nodules in our series was similar to that seen in the Japanese studies, and although we feel that they may play a role in the pathogenesis of carcinoma, we do not believe their presence is necessary for the development of hepatocellular carcinoma.
A prospective, randomized trial of inpatient vs. outpatient bowel preparation for elective colorectal surgery was performed in 100 consecutive patients. Bowel preparation was standardized for both groups and consisted of 4 liters of Colyte (Reed & Carnrick, Piscataway, NJ) and oral neomycin and Flagyl (G. D. Searle & Co., Skokie, IL) the day before surgery. Patients were randomized into four subcategories: ileocolostomy, colocolostomy, abdominal perineal resection, and other. Tap water enemas were administered on the morning of surgery to ensure and adequate mechanical preparation. Ninety-six percent of the inpatient group and 97 percent of the outpatient group were able to drink three-fourths or more of the oral lavage preparation (P = 0.789, Fisher's exact text). A mean of 2.26 tap water enemas was required to achieve clear returns for the inpatient group, compared with 2.28 tap water enemas for the outpatient group (P = 0.221, Fisher's exact test). The adequacy of the bowel preparation as graded by the primary surgeon was good (84 percent), fair (12 percent), and poor (4 percent) in the outpatient group (P = 0.673, Fisher's exact test). Wound infection developed in 4 percent of the inpatient group and 4 percent of the outpatient group (P = 1.0, Fisher's exact test). Anastomotic leak of intra-abdominal abscess was seen in one patient in each group (P = 1.0, Fisher's exact test). We conclude that outpatient bowel preparation is as effective as inpatient bowel preparation for elective colorectal surgery and offers the advantage of cost savings and shorter hospitalization.
Two cases of streptococcal gangrene are reported. Both patients, with hip pain and no obvious source of infection, presented to the same orthopaedic team within a few days. After initial treatment with NSAIDs the outcome was fatal in the cases described. A review of the literature revealed that the administration of NSAIDs may accelerate the course of the disease. The authors conclude that this very rare cause of arthralgia and malaise should be excluded before the administration of NSAIDs for such complaints.
Rats trained to discriminate the anxiogenic compound pentylenetetrazol (PTZ) from water were implanted with osmotic mini-pumps containing 7 mg/kg/day phencyclidine (PCP) or water. Rats were tested for generalization to PTZ 24 hours prior to pump removal, and 4 to 96 hours after pump removal. While the pumps were in place, rats did not generalize to PTZ. When the pumps were removed on day 10, rats in the water group did not generalize to PTZ, but 69% of the rats in the chronic PCP group responded on the PTZ lever at 4 and/or 24 hours after pump removal, suggesting that the PCP withdrawal state mimics the interoceptive cue produced by PTZ. This withdrawal phenomenon was repeatable, in that rats that generalized once to PTZ during PCP withdrawal, generalized a second time when the procedure was repeated. In addition, the phenomenon was dose-dependent, as rats that did not generalize to PTZ after 7 mg/kg/day PCP did generalize when the chronic dose of PCP was increased to 10 mg/kg/day. These findings suggest that there is an anxiogenic component of PCP withdrawal and that tolerance does not develop to this effect.
Migration of an intravascular balloon following embolic therapy for varicocele is uncommon. A third case is reported of migration of a left internal spermatic vein embolic balloon to the right lung in an otherwise healthy twenty-five-year-old male who was treated for a symptomatic left varicocele. The patient, a student naval aviator in the jet pilot program, has had his career adversely affected by this complication.
BACKGROUND: Total skin irradiation for early-stage mycosis fungoides produces clinical remission in 90% of patients, but the median duration of remission is only 2 to 4 years. Etretinate has proven efficacy in advanced mycosis fungoides. Its potential as adjuvant therapy to radiation could be limited by toxicity from the combination. OBJECTIVE: Our purpose was to determine whether oral etretinate at 1 mg/kg can be combined with 35 Gy of radiation without intensifying or prolonging the radiation reaction and to determine the relapse-free survival rate. METHODS: Twenty-three patients began etretinate on day one of radiation and the dose was reduced for nose bleeds, dry skin, or hyperlipidemia. During the reaction skin toxicity questionnaires were completed weekly. Nine concurrent patients receiving only radiation completed identical forms. RESULTS: Etretinate did not intensify the skin reaction but did prolong it by 2 weeks. At a median follow-up of 2 years the relapse-free survival rate in complete responders was similar to stage-matched concurrent and historic control subjects. CONCLUSIONS: Both radiation and etretinate can be given together with acceptable toxicity and without compromising either therapy.
Priming was studied in a task that required a speeded response to photographs of faces. On each trial, subjects viewed two faces and decided if the same person was shown twice or if two different people were shown. Both familiar and unfamiliar (i.e., well-known and unknown) faces were used, and some face pairs were repeated with a mean delay of about 10 min. Repetition was associated with faster reaction times in young subjects (Experiment 1) as well as in amnesic patients and age-matched control subjects (Experiment 2). The patients' reaction times were slower overall, although the magnitude of the priming effect did not differ from that in the control subjects. This preservation of a normal reaction-time facilitation in subjects with impaired recognition memory for faces occurred for both familiar and unfamiliar faces, suggesting that amnesia does not necessarily interfere with the acquisition of new information as indexed by this priming effect.
PURPOSE: The objective of this study was to determine if groin radiation was superior to and less morbid than groin dissection. METHODS AND MATERIALS: Members of the Gynecologic Oncology Group randomized 58 patients with squamous carcinoma of the vulva and nonsuspicious (N0-1) inguinal nodes to receive either groin dissection or groin radiation, each in conjunction with radical vulvectomy. Radiation therapy consisted of a dose of 50 Gray given in daily 200 centiGray fractions to a depth of 3 cm below the anterior skin surface. RESULTS: The study was closed prematurely when interim monitoring revealed an excessive number of groin relapses on the groin radiation regimen. Metastatic involvement of the groin nodes was projected to occur in 24% of patients based on this Group's previous experience. On the groin dissection regimen, there were 5/25 (20.0%) patients with positive groin nodes. These patients received post-operative radiation. There were five groin relapses among the 27 (18.5%) patients on the groin radiation regimen and none on the groin dissection regimen. The groin dissection regimen had significantly better progression-free interval (p = 0.03) and survival (p = 0.04). CONCLUSION: Radiation of the intact groins as given in this study is significantly inferior to groin dissection in patients with squamous carcinoma of the vulva and N0-1 nodes.
In male rats, there is an age-associated decline in the capacity of cardiac sympathetic nerves to release norepinephrine. To investigate whether this phenomenon also occurs in female rats, we examined adrenergic neurochemical transmission in the hearts of female and male Fischer 344 rats. Rats aged 6, 12, and 24 months were employed. Hearts with the right cardiac sympathetic nerve intact were isolated and perfused with Krebs-Ringer solution. Stimulations were performed following the administration of cocaine or metanephrine separately and in combination or following the combination of cocaine, metanephrine, and yohimbine. Cocaine (1 microM) was used to block uptake 1, metanephrine (1 x 10(-5) M) to block uptake 2, and yohimbine (3 microM) to block alpha 2 receptor presynaptically. The nerve was stimulated with frequencies of 2, 6, and 12 Hz, and norepinephrine amount in the effluent was determined by high performance liquid chromatography/electrochemical detection methods. Neither norepinephrine release nor the effects of yohimbine, cocaine, or metanephrine were found to be affected in older female rats (24 month). This suggests that age-related changes in adrenergic neurochemical transmission in the heart of female rats differ from those seen in older male rats.
During the past decade, the multidisciplinary pain clinic has become a popular alternative to the traditional treatment of persistent pain. There is, however, little information describing this population of health care users nor the impact this new demand has on utilization of health care services. The objectives of this study were three fold: to develop a profile of the characteristics of patients referred to a specialty pain clinic including their psychosocial adjustment to their condition; to identify predictors of the use of the specialty services; and to estimate the cost of health service utilization. This historical cohort analytic survey of 571 patients referred to the clinic assessed them for exposure to selected referral variables through a chart review and sampled (n = 222) these patients' current adjustment and health service use through mailed questionnaire. There were four types of use of specialty clinic services. These included: non-users (n = 210); consultation only (n = 180); and the remaining 32% of the referrals were divided between "users-non complete" (n = 98) and "users-complete" (n = 83). "User" groups were similar in characteristics to each other at referral and follow-up on all the major variables with the exception of two factors: non-users lived further from the clinic than users and users were rated as psychologically more vulnerable than non-users. The best predictors for attending the clinic were the presence of referral information from the referring physician and the geographic location of the patient's referring physician. The prevalence of poor psychosocial adjustment was 55.7%, high by comparison with other specialty clinics. Seventy percent of the variance in psychosocial adjustment to chronic pain was explained by social and cognitive variables. In addition, users of specialty pain clinic services generated proportionately less costs in the use of other health services when they were compared to non-users. The importance of social support and meaning of illness variables in predicting psychosocial adjustment to chronic pain is corroborated in this study as is the relevance of the pain clinic cognitive behavioural approach for these problems. In addition, compared to other chronic pain sufferers with similar characteristics, it appears that the use of the pain clinic contains the use of other services and thus has an important economic impact.
The treatment of gastric lymphoma is an area of ongoing controversy. Surgical resection has been the standard therapy. Recent advances, however, have been developed in other treatment modalities. A comparison of treatment options is presented.
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Group analysis is a flexible and effective method of providing group psychotherapy, thereby promoting maturation and symptom relief. Its metapsychology remains incompletely worked out but provides potentially exciting interfaces with biological and physical sciences, through Foulkes's (1973) seminal concept of the group matrix.