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Biomedical subjects

R Wells

Publications and source records attributed to R Wells.

At least 19 recordsLinked to original sources

Osteoblastoma response to chemotherapy.

An 8-year-old boy had an osteoblastoma of the body of C2. After attempted excision, the tumor recurred rapidly and massively. The tumor shrank progressively after treatment with high-dose methotrexate, doxorubicin, and cisplatin. The patient has stopped treatment and been stable for 33 months. Surgical excision remains the treatment of choice for osteoblastoma. Chemotherapy may be useful in selected patients with a recurrent, aggressive tumor or in patients with surgically inaccessible disease.

Bone Neoplasms

Quantifying exposure in occupational manual tasks with cumulative trauma disorder potential.

A method of describing the musculoskeletal loads in the hand and wrist during manual tasks is presented. A profile of twelve factors is used to quantify the exposure of applicable soft tissues to modes of loading suggested as being related to a number of chronic, work-related musculoskeletal disorders such as chronic muscle strain, tenosynovitis, and carpal tunnel syndrome. These factors include estimates of tendon loads and movement, frictional work done on the tendon sheaths, and muscle activation determined using electromyography. The response of these measures to changes of force, repetition, and posture was studied using eight conditions of a simulated task utilizing a pistol grip tool. Measures of tendon frictional work and dynamic electromyographic activity best paralleled the injury outcomes of an epidemiological study using similar task definitions (Silverstein et al. 1986). This field-usable system is being used currently to investigate the relationship between occupational exposure and musculoskeletal disorders.

Biomechanical Phenomena

Intraoperative identification of cardiac patients at risk to develop postoperative atrial fibrillation.

Postoperative atrial fibrillation (AF) is a complication occurring in 11% to 36% of patients after cardiac operations, which results in increased morbidity and hospital costs. A new electrophysiologic screening test was developed to identify those patients at risk for development of postoperative AF. The test was validated in 50 patients (43 men and 7 women) with a mean age of 59.6 +/- 1.3 years who underwent coronary artery bypass grafting with or without other cardiac surgical procedures. After aortic and venous cannulation, but before initiation of bypass, the mid-right atrium was stimulated with a bipolar probe at 25 microA for 3 seconds. Alternating current was increased by 25 microA until AF was induced or up to a maximum of 200 microA. Postoperative AF occurred in 18 patients (36%), 17 of whom had inducible AF (sensitivity = 0.94). Of the remaining 32 AF-free patients, 13 had negative tests (specificity = 0.41). Age and sex were not factors affecting inducibility, although patients who developed AF were older than those who were AF free (63.6 versus 57.3 years, p = 0.02). Length of stay in the intensive care unit was longer for those with postoperative AF than for AF-free patients (3.6 versus 1.9 days, p = 0.02). The negative predictive value of the test was 0.93, and the positive value was 0.47. These data show that this new intraoperative technique may be used to identify patients at risk for postoperative AF. Prophylactic therapy can therefore be directed to only those patients at risk for postoperative AF.

Atrial Fibrillation

Ubiquitin metabolism in ts85 cells, a mouse carcinoma line that contains a thermolabile ubiquitin activating enzyme.

Red blood cell-mediated microinjection was used to introduce radioiodinated ubiquitin into ts85 cells, a mouse cell line that contains a thermolabile ubiquitin-activating enzyme (E1). The proportion of ubiquitin present as histone conjugates, high molecular weight conjugates, and free molecules was then determined by gel electrophoresis and autoradiography. When ts85 cells were incubated at the nonpermissive temperature, 39.5 degrees C, high molecular weight conjugates accumulated. This unexpected result was confirmed by Western blot analyses. To determine whether ubiquitin conjugates formed under nonpermissive conditions or merely persisted after the temperature increase, ts85 cells were incubated at 39.5 degrees C to generate large amounts of conjugates and then shifted to 42 degrees C. The higher temperature resulted in a 25% reduction in conjugates, but upon return to 39.5 degrees C, the ubiquitin conjugates were restored to pre-42 degrees C amounts. Since all changes in ubiquitin conjugate levels occurred above 39.5 degrees C, ts85 cells can couple ubiquitin to cellular proteins even after prolonged culture at nonpermissive temperatures. Western blot analyses showed that less than 10% of the E1 molecules present in ts85 cells at 31 degrees C remained after 2 h at 39.5 degrees C. However, when 125I-ubiquitin was added to extracts from heated ts85 cells an apparent high molecular weight form of E1 and thiol ester adducts between ubiquitin and the E2 carrier proteins were detected by electrophoresis at 4 degrees C. Considering both in vivo and in vitro demonstrations that heated ts85 cells retain the ability to conjugate ubiquitin to endogenous proteins, considerable caution must be exercised in the design and interpretation of proteolysis experiments using this mutant cell line.

Animals

Comparison of genital examination techniques in prepubertal girls.

The results of three separate methods used to examine prepubertal girls are compared and a technique for measuring hymenal orifice diameters from colposcopic photographs is presented. A total of 172 girls who were examined by three techniques during their evaluation in a clinic for suspected child sexual abuse victims were studied. Their ages ranged from 10 months to 11 years with a mean of 5 years, 8 months. The examination techniques used were the supine position with labial separation, the supine position with labial traction, and the knee-chest position. The knee-chest position (98%) and the supine traction method (96%) proved to be superior to the supine separation technique (86%) in opening the vaginal introitus. The largest vertical transhymenal diameters were produced in the knee-chest position, whereas the greatest transverse horizontal spans were generated by the supine traction procedure. Other soft tissue changes were noted but not quantified. A multimethod approach to the examination of the sexually abused child is recommended to take advantage of the strengths of each technique.

Child

Genital findings in prepubertal girls selected for nonabuse: a descriptive study.

This project was designed to collect normative data on the genital anatomy from a sample of nonabused prepubertal girls. A total of 114 girls between the ages of 10 months and 10 years were examined and photographed with a colposcope. After screening for the onset of puberty and the possibility of undetected abuse, 93 subjects remained. Examination techniques included a supine labial separation approach, a supine labial traction method, and a prone knee-chest position. Common genital finding included erythema of the vestibule (56%), periurethral bands (50.6%), labial adhesions (38.9%), lymphoid follicles on the fossa navicularis (33.7%), posterior fourchette midline avascular areas (25.6%), and urethral dilation with labial traction (14.9%). The hymenal orifice opened more frequently during the knee-chest (95.2%) and the labial traction (90.5%) methods than with the supine separation (79.3%) approach. Hymenal findings included mounds (33.8%), projections (33.3%), and "septal remnants"/midline hymenal tags (18.5%). Intravaginal findings of vaginal ridges (90.2%) and rugae (88.7%) were found primarily through the labial traction approach. The cervix was visualized without the use of speculum in 69% of the children during the knee-chest examination. Unusual findings included posterior fourchette friability (4.7%), anterior hymenal clefts (1.2%), and notches of the hymen (6%). One child had an imperforate hymen (1.2%) and 2 (2.5%) had hymenal septa. A vaginal discharge was detected in 2 (2.6%) and a foreign body in 1 (1.3%). Tables that include the vertical and horizontal hymenal orifice diameters by age group and by method are presented.

Child

Maternal drug use and risk of childhood nonlymphoblastic leukemia among offspring. An epidemiologic investigation implicating marijuana (a report from the Childrens Cancer Study Group).

The Childrens Cancer Study Group conducted a case-control study designed to assess in utero and postnatal exposures in children with acute nonlymphoblastic leukemia (ANLL). Analyses were performed for reported maternal use of medications and drugs in the year preceding and during the index pregnancy of the 204 case-control pairs. An 11-fold risk (P = 0.003) was found for maternal use of mind-altering drugs just prior to or during the index pregnancy. Compared with ANLL cases not exposed to marijuana, exposed cases were significantly younger at diagnosis of ANLL (P less than 0.01) and were more often of the myelomonocytic and monocytic subtypes (P less than 0.01). Use of antinausea medication for more than 11 weeks was also associated with a significantly elevated relative risk of 2.81 and a dose-response relationship was noted (P = 0.05 for trend). These results suggest that maternal drug use of marijuana may have an etiologic role in childhood ANLL and may be specific for morphologically defined subgroups.

Adolescent

Perianal findings in prepubertal children selected for nonabuse: a descriptive study.

The results of the perianal portion of a project designed to collect normative data of the anogenital anatomy from a representative sample of prepubertal children is presented. A total of 318 children were examined by three physicians from a child sexual abuse evaluation program. After screening for the onset of puberty and the possibility of undetected abuse, 267 subjects remained. The sample included 161 girls and 106 boys ranging in age from 2 months to 11 years. The perianal findings that were encountered with the greatest frequency included erythema (41%), increased pigmentation (30%), and venous engorgement (52%) after two minutes in the knee-chest position. Wedge-shaped smooth areas in the midline, with or without depressions, were found both anterior and posterior to the anus in 26% of the children. Anal skin tags/folds were discovered anterior to the anus in 11%. In 49% of the children there was some dilatation of the anus which opened and closed intermittently in 62%. Flattening of the anal verge and rugae occurred during dilatation by the midpoint of the examination in 44% and 34%, respectively. Perianal findings that were found infrequently in all subgroups included skin tags/folds (0%) and scars (1%) outside the midline, anal dilatation greater than 20 mm without the presence of stool in the rectal ampulla (1.2%), irregularity of the anal orifice after complete dilatation (3%), and prominence of the anal verge (3%). No abrasions, hematomas, fissures, or hemorrhoids were encountered. Less commonly detected findings within specific subgroups included perianal erythema in girls (32%) as compared to boys (57%), pigmentation in the lighter skinned white children (22%) when compared to black (53%) and Hispanic (58%) children, and venous congestion at the beginning of the examination (7%) when compared to the same findings after four minutes in the knee-chest position (73%). There were no perianal skin tags/folds found in the boys. The relatively high incidence of perianal soft tissue changes that were found in this study, when compared to the frequency of similar observations in children suspected of having been sexually abused, reemphasizes the caution medical examiners must exercise in rendering an opinion as to the significance of medical findings.

Anal Canal

Nursing and AIDS.

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Acquired Immunodeficiency Syndrome

Lumbrical muscle function as revealed by a new and physiological approach.

The lumbrical muscle is clearly one of several possible extensors of the interphalangeal joints. With an origin on the flexor digitorum profundus tendon it is credited with unloading the elastic tension across the interphalangeal joints and thereby facilitating their extension. Its role at the metacarpophalangeal joint is not a matter of universal agreement. Attempts to simulate its action with weights over pulleys have not clarified this role, since true simulation would require the development of a means of applying force along the course of the lumbrical without pre-determining which end would move. Such a system is herein described; it uses a Bowden cable, which is commonly used to activate the brakes of a bicycle. After constructing length-tension curves of the profundus muscle in four fresh cadavers prior to the onset of rigor mortis, the interaction of realistic lumbrical loads with profundus elastic tension was studied. By contraction a lumbrical muscle adds a small but significant flexor force at the metacarpophalangeal joint, and thereby it is also capable of contributing to radial deviation and possibly rotation. As it runs from a flexor tendon to an extensor tendon and is endowed with a great many muscle spindles, the lumbrical could play a part in the control of finger movement by monitoring the rate of hand closing during grasp.

Fingers

Biologic characteristics and treatment of acute nonlymphocytic leukemia in children. Report of the ANLL Strategy Group of the Childrens Cancer Study Group.

Today approximately 75 per cent of children with ANLL can be induced into a complete remission and approximately 40 per cent will have an event-free survival for more than 3 years, irrespective of whether they received a bone marrow transplantation or chemotherapy after induction. In order to achieve these results very intensive therapy is required. The morbidity and mortality of treatment are high. The length of therapy needed after induction of remission is not known. Whether or not maintenance therapy is required is perhaps related most directly to the intensity of the therapy employed. Similarly, the role of bone marrow transplantation in patients in first remission, treatment of CNS leukemia, and treatment of chloromas are controversial. There is general agreement that WBCs over 100,000, acute monoblastic leukemia in infants less than 2 years of age, and certain chromosomal abnormalities are associated with a poor prognosis. Although there has been a dramatic improvement in the treatment of ANLL over the past 15 years, stratification of therapy based on biologic parameters, and alteration of treatment based on the early responses to treatment may be required before further advances will be made.

Acute Disease

The AIDS challenge.

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Acquired Immunodeficiency Syndrome

Amino acid sequences common to rapidly degraded proteins: the PEST hypothesis.

The amino acid sequences of ten proteins with intracellular half-lives less than 2 hours contain one or more regions rich in proline (P), glutamic acid (E), serine (S), and threonine (T). These PEST regions are generally, but not always, flanked by clusters containing several positively charged amino acids. Similar inspection of 35 proteins with intracellular half-lives between 20 and 220 hours revealed that only three contain a PEST region. On the basis of this information, it was anticipated that caseins, which contain several PEST sequences, would be rapidly degraded within eukaryotic cells. This expectation was confirmed by red blood cell-mediated microinjection of 125I-labeled caseins into HeLa cells where they exhibited half-lives of less than 2 hours. The rapid degradation of injected alpha- and beta-casein as well as the inverse correlation of PEST regions with intracellular stability indicate that the presence of these regions can result in the rapid intracellular degradation of the proteins containing them.

Amino Acid Sequence