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Biomedical subjects

E Watkins

Publications and source records attributed to E Watkins.

At least 19 recordsLinked to original sources

Equivalent dose of ephedrine and phenylephrine in the prevention of post-spinal hypotension in Caesarean section.

BACKGROUND: Comparative studies of ephedrine and phenylephrine in prevention of hypotension after spinal anaesthesia for Caesarean section have lacked a consensus on dose equivalence. The aim of this study was to determine the minimum vasopressor dose for each of these drugs to calculate the dose ratio for clinical equivalence in the prevention of hypotension. METHODS: Patients with a normal singleton pregnancy beyond 36 weeks gestation undergoing elective Caesarean section under spinal anaesthesia were randomized into two groups. The first patient in Group A received 50 mg of ephedrine in saline 0.9% w/v, 500 ml, at 999 ml h(-1), the maximum rate possible on the pump and the first patient in Group B received 500 microg of phenylephrine in saline 0.9% w/v, 500 ml, at the same rate. The initial dose for dilution was an arbitrary choice. The dose of vasopressor in the saline bag for every subsequent patient was established by the efficacy of the dose in preventing hypotension in the previous patient according to the technique of up-down sequential allocation. Minimum vasopressor dose for each drug was determined according to the Dixon-Massey formula. RESULTS: The minimum vasopressor dose in saline 500 ml was 532.9 microg (95% CI 506.0-559.8) for phenylephrine and 43.3 mg (95% CI 39.2-47.3) for ephedrine. The concentration needed for equivalence at an infusion rate of 999 ml h(-1) was 1.07 microg ml(-1) for phenylephrine and 86.66 microg ml(-1) for ephedrine. Mean (sd) dose used for phenylephrine was 496.45 (78.3) microg and for ephedrine 39.64 (6.33) mg. CONCLUSION: This study demonstrates a potency ratio of 81.2 (95% CI 73.0-89.7) for equivalence between phenylephrine and ephedrine in prevention of hypotension after spinal anaesthesia for Caesarean section.

Adolescent↗

Characterization of avian influenza virus isolates submitted to the National Centre for Foreign Animal Disease between 1997 and 2001.

The National Centre for Foreign Animal Disease (NCFAD) in Winnipeg, Manitoba, is the Canadian Food Inspection Agency's (CFIA) newest high biocontainment laboratory. One of the functions of the NCFAD is to serve as a national reference laboratory for avian influenza. Between 1997 and 2001, 15 avian influenza virus isolates were characterized. These isolates originated from domestic poultry, imported caged birds held in quarantine, and wild birds. Diagnostic specimens were submitted to the NCFAD by CFIA field veterinarians, provincial veterinary diagnostic laboratories, and veterinary colleges. Characterization of isolates included the determination of H and N subtypes: H1, H6, H7, and H10 subtypes were isolated from domestic poultry; H3, H4, and three H13 viruses were isolated from water fowl, and six H3 viruses were isolated from caged birds being held in import quarantine. Selected isolates were characterized with respect to their pathogenic potential by intravenous inoculation of 4-to-6-wk-old chickens. A molecular-based protocol was used to assess the pathogenicity of one H7 isolate. During this period, work was also carried out toward validating our molecular pathotyping protocol for avian influenza viruses with H5 and H7 hemagglutinin subtypes.

Amino Acid Sequence↗

Rumination and executive function in depression: an experimental study.

BACKGROUND: Major depression is associated with cognitive deficits, particularly those requiring central executive functioning. Depressed patients also tend to focus on and think about their symptoms and problems ("ruminate") more than non-depressed controls. Although an association has been found between rumination and impaired performance on a central executive processing task, the causal relation between impaired executive functioning and rumination has not been determined. This study sought to directly manipulate rumination and assess the impact on executive functioning in depression as measured by random number generation. METHODS: Depressed patients (n=14) and non-depressed controls (n=14) were compared on a random number generation task, performed after both a rumination induction and after a distraction induction, with order of inductions counter balanced within each group. RESULTS: Compared with the distraction induction, the rumination induction produced a significant increase in both ruminations and the tendency towards stereotyped counting responses (thought to reflect a failure of inhibitory executive control) in depressed patients but not in controls. However, after distraction, no difference in random number generation or rumination was found between the two groups. CONCLUSIONS: The aspects of executive function involved in random number generation are not fundamentally impaired in depressed patients. In depressed patients, the rumination induction seems to trigger the continued generation of ruminative stimulus independent thoughts, which interferes with concurrent executive processing.

Adult↗

Rumination and overgeneral memory in depression: effects of self-focus and analytic thinking.

Previous research has shown that, compared with a rumination induction, a brief distraction procedure reduces overgeneral autobiographical memory in depression. The authors investigated whether this effect depends on reductions in analytic thinking or reductions in self-focus. Focus of attention (high vs. low self-focus) and thinking style (high vs. low analytical thinking) were independently manipulated in depressed patients in a 2 x 2 design. Autobiographical recall was measured pre- and postmanipulation. Thinking style significantly affected overgeneral memory, whereas focus of attention significantly affected despondent mood. Reducing analytical self-focus reduced overgeneral memory, suggesting that high levels of naturally occurring ruminative analytic thinking may be important in the maintenance of overgeneral memory. Overgeneral memory in depression may be associated with chronic ruminative attempts to make sense of current or past difficulties.

Adolescent↗

Decentring and distraction reduce overgeneral autobiographical memory in depression.

BACKGROUND: Increased recall of categorical autobiographical memories is a phenomenon unique to depression and post-traumatic stress disorder, and is associated with a poor prognosis for depression. Although the elevated recall of categorical memories does not change on remission from depression, recent findings suggest that overgeneral memory may be reduced by cognitive interventions and maintained by rumination. This study tested whether cognitive manipulations could influence the recall of categorical memories in dysphoric participants. METHODS: Forty-eight dysphoric and depressed participants were randomly allocated to rumination or distraction conditions. Before and after the manipulation, participants completed the Autobiographical Memory Test, a standard measure of overgeneral memory. Participants were then randomized to either a 'decentring' question (Socratic questions designed to facilitate viewing moods within a wider perspective) or a control question condition, before completing the Autobiographical Memory Test again. RESULTS: Distraction produced significantly greater decreases in the proportion of memories retrieved that were categorical than rumination. Decentring questions produced significantly greater decreases in the proportion of memories retrieved that were categorical than control questions, with this effect independent of the prior manipulation. CONCLUSIONS: Elevated categorical memory in depression is more modifiable than has been previously assumed; it may reflect the dynamic maintenance of a cognitive style that can be interrupted by brief cognitive interventions.

Adult↗

Immunogenicity of a 'pre-S2 plus S' hepatitis B vaccine in healthy adults.

The product of the pre-S plus S gene of hepatitis B virus appears to be more immunogenic in mice than the S-gene product (HBsAg) alone. Therefore, we tested the immunogenicity in healthy adults of a hepatitis B vaccine containing the 'middle protein' gene product of pre-S2 plus S (pre-S vaccine). We compared the immunogenicity of three doses of the pre-S vaccine with that of a commercially available recombinant hepatitis B vaccine (Recombivax-HB); 87 seronegative adults were randomized to receive 12 micrograms (group 1), 24 micrograms (group 2), or 48 micrograms (group 3) of the pre-S vaccine or 10 micrograms of Recombivax-HB (group 4) by deltoid injection at 0, 1 and 6 months. Antibody to HBsAg (anti-HBs) appeared after booster vaccination in > or = 94% of vaccinees. Immunogenicity was best in recipients of 48 micrograms of the pre-S vaccine and Recombivax-HB, and geometric mean titres (GMT) for the pre-S vaccine were higher than those for Recombivax-HB only at the pre-S vaccine dose of 48 micrograms (group 3). Antibody to pre-S2 developed in 75% of the pre-S2 vaccine recipients (not in Recombivax-HB recipients) within 7 months. These findings indicate that the pre-S vaccine is immunogenic in healthy adults but that a dose of 48 micrograms of the current formulation is required to equal or exceed the immunogenicity of currently available, recombinant S-only vaccine. Studies in non-responders to S-only vaccines will be necessary to define an immunological advantage of the pre-S vaccines, and additional assessments will be necessary to determine whether anti-pre-S2 enhances protective efficacy.

Adult↗

Staging of carcinoma of the esophagus and cardia: a comparison of different staging criteria.

The third edition [1988] of the Manual for Staging of Cancer of the American Joint Committee on Cancer (AJCC) was developed to permit finer discrimination between stages than was true of the previous edition [1983]. This study was designed to determine whether or not this goal was achieved. Pathologic staging of the specimens removed from 265 patients with carcinoma of the esophagus or cardia undergoing esophagogastrectomy between 1970 and 1988 was performed according to criteria published in the second and third editions and their survival data compared. The new staging criteria of the AJCC provides no better discrimination of stages according to survival than was true of the earlier version, the 5-year survival of stage IIA patients being similar to that of stage I patients (37.5 +/- 6.7% vs. 50.8 +/- 17.7%), and the survival of stage IIB patients being similar to that of stage III patients (16.2 +/- 8.1% vs. 13.6 +/- 3.7%). However, depth of wall penetration and extent of lymph node involvement were reliable independent predictors of survival. We propose a modified version of the Skinner WNM staging plan that provides a modest increase in staging fragmentation.

Actuarial Analysis↗

Ten to 20-year clinical results after short esophagomyotomy without an antireflux procedure (modified Heller operation) for esophageal achalasia.

To determine the long-term clinical results after modified esophagomyotomy without an antireflux procedure for esophageal achalasia, the status of all patients undergoing this operation with a minimum follow-up time of 10 years was reviewed; 81 such patients were operated on between January 1970 and January 1981. Thirteen patients were lost to follow-up review permitting clinical evaluation during the past year of 68 patients (84%) observed for a median of 13.6 years. Fifty-nine patients (87%) were improved by operation; 90% of the patients who underwent a primary procedure were improved, whereas only 73% of patients undergoing reoperation benefited. Kaplan-Meier analysis of the results of all 81 patients disclosed an improvement rate of 98.5% at 5 years, 95.6% at 10 years, 85.8% at 15 years, and 67.3% at 20 years. When the level of improvement or lack thereof was analyzed, the percentage of excellent results decreased from 54% to 32% (P = 0.02). The percentage of good results remained the same, whereas fair or poor results together increased from 20% to 37% (P = 0.05). Neither age, sex, esophageal caliber, duration of symptoms, or previous therapy appeared to influence these results. We conclude that limited esophagomyotomy without an antireflux procedure results in persistent long-term improvement for the patient with esophageal achalasia. The level of improvement, however, decreases with the passage of time, presumably because of persistent disease in the body of the esophagus leading to impaired esophageal emptying in some patients and late reflux esophagitis in other patients owing to poor esophageal clearance.

Adolescent↗

Maternal care coordination for migrant farmworker women: program structure and evaluation of effects on use of prenatal care and birth outcome.

Nearly three fourths of the migrant farmworkers in the U.S. are Hispanic. Cultural and social barriers, along with constant travel, make coordination of care a significant concern for migrant health centers providing perinatal services to female farmworkers. As part of a demonstration project, a migrant-specific maternal care coordination program was developed that used bilingual staff, outreach services, lay health advisers, and a multistate tracking system. Following the initiation of the project, first-trimester entry into prenatal care and number of prenatal visits increased over a five-year period among the target population. Successful tracking methods provided outcome data on more than 80 percent of participants during the project period. The results of this study suggest that migrant health centers should focus on employing public health-oriented bilingual or bicultural health professionals and that an outreach strategy must be an integral part of a health care delivery system serving migrant farmworkers. Without these key ingredients, health care services will not be accessible or acceptable for this hard-to-reach population. Collaboration among the National Migrant Resource Program, the Migrant Clinicians Network, and the National Perinatal Association can facilitate development of a regionwide perinatal service system for female migrant farmworkers.

Communication Barriers↗

Barrett's esophagus. Prevalence and incidence of adenocarcinoma.

Between January 1973 and January 1989, 241 patients with Barrett's esophagus were treated at the Lahey Clinic Medical Center, Burlington, Mass. Of these patients, 65 presented with adenocarcinoma in Barrett's esophagus for a prevalence rate of 27%. Of 176 patients followed up for a total of 497 patient-years, adenocarcinoma developed in five patients for an incidence of one per 99 patient-years. The development of adenocarcinoma during endoscopic surveillance 1, 2, 2, 4, and 10 years after the initial diagnosis of Barrett's esophagus emphasizes the importance of long-term endoscopic and histologic surveillance. All five patients had severe dysplasia before adenocarcinoma developed. Yearly endoscopic follow-up examination is recommended for all patients with Barrett's esophagus unless mild dysplastic changes are found, in which case surveillance should be increased. Patients with severe dysplasia who are otherwise acceptable candidates for operation should be advised to have esophageal resection.

Adenocarcinoma↗

Pathologic review of consecutive radical prostatectomy specimens. Nerve sparing versus nonnerve sparing.

Retrospective pathologic analysis was conducted of specimens from 88 radical retropubic prostatectomy operations performed between 1982 and 1987 inclusive. The median age of patients was sixty years (range, 46 to 73 years). Of the 88 radical prostatectomies performed, 51 were nerve-sparing (40 bilateral) and 37 were nonnerve-sparing (11 unilateral) procedures. Preoperative clinical staging was similar in both groups. Thirty-five of 37 patients (95%) in nonnerve-staging group and 51 of 51 patients (100%) in nerve-sparing group had clinical Stage B2 disease or less. Pathologic staging in both groups was also similar. In 26 of 37 patients (70%) in nonnerve-sparing group and in 35 of 51 patients (69%) in nerve-sparing group, disease remained localized to the prostate. Both groups were analyzed retrospectively to determine whether or not the incidences of microinvasion of capsule and of extraprostatic disease differed. Review of the apical and lateral margins of the specimens revealed no statistically significant difference in either the degree of microinvasion of capsule or the incidence of extraprostatic disease between the groups.

Adenocarcinoma↗

Adenocarcinoma in Barrett's esophagus. A clinicopathologic study of 65 cases.

The natural history of Barrett's esophagus, particularly the prevalence and incidence of malignant changes in it, remains controversial. Furthermore the prognosis of surgically treated patients with carcinoma in Barrett's esophagus has not been elucidated fully. To examine these and other issues, the records of 65 patients with carcinoma in Barrett's esophagus presenting at the Lahey Clinic Medical Center from January 1973 to January 1989 were reviewed. During this period, 241 patients with documented Barrett's esophagus were seen, for a prevalence of carcinoma of 27%. Adenocarcinoma in Barrett's esophagus accounted for 30% of the surgically treated carcinomas of the thoracic esophagus during this period. All but four of these patients were men. Symptoms of chronic reflux were present in less than one half of the patients and dysphagia was often the presenting symptom. In eight patients the carcinoma was discovered on routine surveillance endoscopy, and in four patients progression of disease from benign columnar epithelium to dysplasia to carcinoma was documented. Tumors developed in six patients who had undergone previous antireflux surgery, and in four other patients a second carcinoma developed in residual Barrett's epithelium after a previous resection. Of the 65 patients, 61 (94%) were considered to have operable disease, all of whom underwent resection. Two patients (3.3%) died within 30 days of operation. The resected specimens were staged as follows: stage 0, 4; stage I, 10; stage II, 17; stage III, 25; stage IV, 4. Of the resected specimens, 73% showed areas of dysplasia adjacent to the tumor. The overall adjusted actuarial 5-year survival rate was 23.7%. The 3-year survival rate was 100% for patients with stage 0 carcinoma, 85.7% for patients with stage I carcinoma, 53.6% for patients with stage IIA carcinoma, 45% for patients with stage IIB carcinoma, 25.2% for patients with stage III carcinoma, and 0% for patients with stage IV carcinoma. The premalignant nature of Barrett's esophagus requires endoscopic surveillance to detect early carcinoma because symptoms often occur late or are absent. Antireflux surgery does not protect against the development of carcinoma. All of the Barrett's epithelium must be resected because a second carcinoma may develop in residual columnar epithelium. Severe dysplasia should be considered an indication for resection. Although operability and resectability rates are high, long-term survival is not. Early detection is mandatory if long-term survival is to be achieved.

Adenocarcinoma↗

Long-term results of pancreatic resection and segmental pancreatic autotransplantation for chronic pancreatitis.

Thirteen patients who underwent extensive pancreatic resection and segmental autotransplantation and who have a median follow-up of 62 months are presented. Eleven patients had technically successful grafts. Three of six patients who underwent total pancreatectomy and three of five patients who underwent near-total resection remain insulin-independent. Those patients who require insulin require small doses and have stable diabetes. Pain has recurred in 7 of the 11 patients who underwent distal subtotal resection; 5 of them required pancreatoduodenectomy and completion pancreatectomy for pain relief. Because of the high rate of recurrence of pain after distal resection, we favor pancreatoduodenectomy as the initial procedure of choice. When distal near-total or total pancreatectomy is required, the addition of segmental autotransplantation offers definitive, although at times transient, benefits in glucose homeostasis compared with no transplantation.

Adult↗

Recombinant-yeast-derived hepatitis B vaccine in healthy adults: safety and two-year immunogenicity of early investigative lots of vaccine.

We tested the safety and long-term immunogenicity of two of the early investigative lots of a recombinant-yeast-derived hepatitis B vaccine in immunocompetent adults. Three 10-micrograms doses of recombinant hepatitis B vaccine (Merck Sharp & Dohme Research Laboratories, West Point, PA) were administered by deltoid intramuscular injection at time 0, 1, and 6 months to 65 seronegative adult health workers. Following a complete three-injection course, 98% of vaccinees acquired anti-HBs, 97% at levels greater than 10 mlU/ml, and 95% maintained such "protective" antibody levels at 1 year. At 2 years, 93% retained antibody, but only 68% had levels greater than 10 mlU/ml. In those who responded to vaccination by achieving any detectable level of antibody, the peak geometric mean titer of anti-HBs, measured at 9 months, was 741 +/- 6 mlU/ml; the geometric mean titer fell to 348 +/- 6 at 1 year and to 66 +/- 7 at 2 years. Side effects were trivial, and levels of yeast antibody, as measured by radioimmunoassay, were not changed from prevaccine levels. No serious adverse effects were encountered, and neither type B nor non-B hepatitis occurred in any vaccine. These findings demonstrate that the recombinant yeast hepatitis B vaccine is safe and immunogenic but that 10 micrograms of the early investigative lots of the recombinant vaccine is less immunogenic than 20 micrograms of the plasma-derived vaccine. Recipients of early investigative vaccine lots should be considered for booster vaccination with currently available, more immunogenic vaccine lots.

Adult↗

Intensive combined modality therapy of small round cell and undifferentiated sarcomas in children and young adults: local control and patterns of failure.

Seventy-five patients (ages 4-35 years) with the following small round cell tumors and undifferentiated sarcoma were treated at the National Cancer Institute: Ewing's sarcoma (n = 32), peripheral neuroepithelioma (n = 14), rhabdomyosarcoma (n = 24), undifferentiated sarcoma (n = 5). Most patients had poor prognostic features including 36 (48%) with metastatic disease, and 42 (56%) with central (truncal) tumors (22 in the pelvis). Treatment included 5 cycles of intensive induction chemotherapy with vincristine, cyclophosphamide and adriamycin, plus aggressive local radiation therapy using simulation and computerized treatment planning for all patients. Thereafter, complete clinical responses were consolidated with intensive chemotherapy, total body irradiation and autologous bone marrow transplantation. There were three local only failures, 10 local plus distant failures, 36 distant only failures, 3 treatment-related deaths, and one intercurrent death. Overall actuarial survival and event-free survival at 4 years are 49 and 29%, respectively. Actuarial freedom from local progression was seen in 74% of patients at 4 years, quite remarkable considering the bulk and location of most of these tumors. Without aggressive surgery, many of these high risk patients had satisfactory outcomes, but better systemic treatments are still needed.

Adolescent↗

Structure of an ectodermally expressed sea urchin metallothionein gene and characterization of its metal-responsive region.

The metallothionein-A gene in the metallothionein gene family of the sea urchin Strongylocentrotus purpuratus (SpMTA gene) was sequenced and found to contain three coding exons plus a 3' entirely noncoding exon. Putative alpha and beta MT domains were encoded, by its exons 2 and 3, respectively, in reverse of the order in vertebrate metallothionein genes. The SpMTA promoter was characterized through the expression of recombinant constructs containing various portions of the proximal 678-base-pair (bp) 5'-flanking region of the SpMTA gene. Zygotes injected with constructs were cultured to the blastula stage in the presence of a heavy-metal chelator and then incubated in the presence or absence of cadmium. The longest constructs were expressed only when heavy-metal ion was present. Two putative metal-responsive elements (MREs a and b) within 240 bp of the transcription start site resembled mammalian MREs in their critical 8-bp cores (TGCRCNCS) and in their locations relative to each other and to the TATA box. Elimination of activity by site-specific mutations in MREs a and b, separately or in both, identified them as metal regulatory elements. Thus, MRE recognition in this invertebrate resembles that in vertebrates. Upstream sites with single-mismatched MREs neither acted as MREs nor amplified the activity of MREs a and b. The SpMTA, Spec1, and CyIIIa actin genes, which have the same ectodermal specificity, have common DNA elements at relatively similar locations in their promoter regions; however, these elements are insufficient in themselves to promote gene expression.

Amino Acid Sequence↗

Limited esophagogastrectomy for carcinoma of the cardia. Indications, technique, and results.

Between 1970 and 1988, 149 patients with carcinoma of the cardia were operated on at the Lahey Clinic. Of these patients, 127 (85%) underwent resection; 23 (18.1%) were of a palliative nature. More than 75% had Stage III and IV disease. One patient (0.8%) died within 30 days of the operation of a myocardial infarct. Two other patients failed to leave the hospital. Of 25 postoperative complications, 14 (11%) were considered major. Palliation of dysphagia was successful in 80% of patients. The actuarial 5-year survival rate was 22.4%. Of patients with Stage I and II disease, 36.6% survived for 5 years, and of patients with Stage III disease, 22.5% survived. No patient with Stage IV disease lived for longer than 1 year. It is concluded that limited esophagogastrectomy can be performed in most patients with carcinoma of the cardia with low mortality and morbidity and with satisfactory long-term survival.

Adenocarcinoma↗