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Biomedical subjects

H Goodman

Publications and source records attributed to H Goodman.

At least 19 recordsLinked to original sources

Analysis of 1.9 Mb of contiguous sequence from chromosome 4 of Arabidopsis thaliana.

The plant Arabidopsis thaliana (Arabidopsis) has become an important model species for the study of many aspects of plant biology. The relatively small size of the nuclear genome and the availability of extensive physical maps of the five chromosomes provide a feasible basis for initiating sequencing of the five chromosomes. The YAC (yeast artificial chromosome)-based physical map of chromosome 4 was used to construct a sequence-ready map of cosmid and BAC (bacterial artificial chromosome) clones covering a 1.9-megabase (Mb) contiguous region, and the sequence of this region is reported here. Analysis of the sequence revealed an average gene density of one gene every 4.8 kilobases (kb), and 54% of the predicted genes had significant similarity to known genes. Other interesting features were found, such as the sequence of a disease-resistance gene locus, the distribution of retroelements, the frequent occurrence of clustered gene families, and the sequence of several classes of genes not previously encountered in plants.

Arabidopsis

Enhanced lymphoproliferation and diminished autoimmunity in CD4-deficient MRL/lpr mice.

MRL/lpr mice spontaneously develop an autoimmune disease with features of systemic lupus erythematosus. They also develop a lymphoproliferative disorder characterized by a massive accumulation of double-negative (DN) T cells that lack both CD4 and CD8. To clarify the role of CD4 in autoimmunity and lymphoproliferation in these mice, CD4-deficient MRL/lpr mice were generated. CD4-deficient MRL/lpr mice developed massive expansion of DN T cells in the blood, spleen, and lymph nodes, which significantly exceeded the degree of lymphoproliferation in CD4-expressing control MRL/lpr mice. Despite this lymphoproliferation, CD4-deficient MRL/lpr mice produced little, if any, antibodies to double-stranded DNA, and they had prolonged survival relative to CD4-expressing littermates. However, they eventually developed moderately severe nephritis, characterized by immunoglobulin and complement deposition in glomeruli, vasculitis, and renal infiltration by CD8+ T cells. These findings indicate that (1) lymphoproliferation in MRL/lpr mice does not require the expression of CD4; (2) autoantibody production in MRL/lpr mice is dependent on the expression of CD4 and not on the accumulation of DN T cells; and (3) the development of nephritis in MRL/lpr mice involves both CD4-dependent and CD4-independent mechanisms.

Animals

Patients' perceptions of their education needs in the first six weeks following discharge after cardiac surgery.

The aim of this study was to discover what information and support patients feel they need in the 6-week rehabilitation period following discharge after cardiac surgery. It was undertaken at the request of the hospital multidisciplinary cardiac rehabilitation team to enable them to plan a package of information to meet those needs. It was a local study aiming to gain insight into the patients' own views by asking them to keep a diary over the 6-week period and then take part in an unstructured interview when they returned for their 6-week out-patient appointment. The analysis of the respondents' comments gave an insight into their whole experience of the first 6 weeks following discharge. The themes which emerged were wide-ranging and were grouped under the headings of the early discharge needs of pain relief and sleep promotion, psychological needs, practical needs and community support. To take the study forward, several recommendations were made to improve the rehabilitation experience. These included additions to the literature and patient education sessions, and changes to ensure a smoother transition into the community. The findings also suggest the need for improvements in and further research into the whole area of the psychological preparation for discharge after cardiac surgery.

Activities of Daily Living

Geriatric rehabilitation.

The United States population is aging, and the number of people over age 85 is expected to quadruple early in the next century. Advancing age increases the likihood of aquiring a disabling condition. By the next century, every other visit to a health provider will be made by an elderly person. Nurse practitioners will see increasing numbers of older patients. They will be called on to differentiate normal aging states from pathological conditions. A focus on promoting vigorous aging, minimizing disabling conditions, and restoring or preserving function and independence will assist the practitioner in appropriate evaluation and treatment of the elderly.

Accidental Falls

Acute-phase response and the hypercoagulable state in pulmonary tuberculosis.

In our experience, severe pulmonary tuberculosis (PTB) is often complicated by deep venous thrombosis (DVT). Because of the association between inflammation and haemostatic changes that can result in a hypercoagulable state, we have prospectively examined such predisposing factors in representative patients. Sequential analyses in a control group with active PTB showed anaemia, thrombocytosis, elevations in plasma fibrinogen, fibrin(ogen) degradation products (FDP), tissue plasminogen activator (t-PA) and inhibitor (PAI-1) with depressed antithrombin III levels. Age, sex and disease matched individuals with venographically proven DVT had higher FDP (15.8 +/- 14.3 v 3.2 +/- 1.7 micrograms/ml:P < 0.01), t-PA (19.4 +/- 14.9 v 11.3 +/- 0.8 ng/ml:P < 0.01), and functional PAI-1 activity (11.6 +/- 6.3 v 4.2 +/- 4.1:P < 0.01) with lower platelet counts (347 +/- 110 v 563 +/- 230 x 10(9)/1:P < 0.01). Fibrinogen levels in all patients rose during the first 2 weeks of therapy and, together with related disturbances, corrected within 12 weeks. In conclusion, elevated plasma fibrinogen with impaired fibrinolysis coupled with a decrease in antithrombin III and reactive thrombocytosis would appear to favour the development of DVT in PTB.

Acute-Phase Reaction

Geriatric rehabilitation.

The United States population is aging, and the number of people over age 85 is expected to quadruple early in the next century. Advancing age increases the likelihood of acquiring a disabling condition. By the next century, every other visit to a health provider will be made by an elderly person. Nurse practitioners will see increasing numbers of older patients. They will be called on to differentiate normal aging states from pathological conditions. A focus on promoting vigorous aging, minimizing disabling conditions, and restoring or preserving function and independence will assist the practitioner in appropriate evaluation and treatment of the elderly.

Aged

Phase I pharmacokinetic study of the hypoxic cell sensitizer etanidazole with carboplatin and cyclophosphamide in the treatment of advanced ovarian cancer.

PURPOSE: A Phase I study was undertaken to determine the maximum tolerated dose of the hypoxic cell sensitizer etanidazole which could be administered with carboplatin and cyclophosphamide, to determine whether adequate serum levels of etanidazole were achieved to allow for alkylating agent sensitization, and whether pretreatment with etanidazole altered carboplatin pharmacokinetics. METHODS AND MATERIALS: Patients received 2 g/m2 of intravenous etanidazole followed by a second dose of 4 g/m2 90 min later, followed by intravenous carboplatin (300 mg/m2) and cyclophosphamide (600 mg/m2) for four treatment cycles. Patients received an additional two cycles of carboplatin and cyclophosphamide without etanidazole. RESULTS: Two patients who received a total of 24 g/m2 of etanidazole developed Grade 1 neurotoxicity, and therefore etanidazole doses were not escalated further. The grade of granulocytopenia was worse after cycles with etanidazole than after those without (p = 0.03), but clinical outcome was not different. Etanidazole levels were adequate for alkylating agent sensitization (> 70 ug/ml) in all patients for the majority of the 7 h of testing. Pharmacokinetic data suggested t1/2 alpha and t1/2 beta for carboplatin were prolonged after pretreatment with etanidazole. CONCLUSION: Etanidazole, 2 g/m2 followed by 4 g/m2 90 min later, is safe and results in adequate serum levels for alkylating agent sensitization. Neurotoxicity appears to prevent dose escalation of etanidazole, and an interaction between etanidazole and carboplatin may have enhanced neurotoxicity in these patients.

Antineoplastic Combined Chemotherapy Protocols

Analysis of HPV-positive and -negative vulvar carcinomas for alterations in c-myc, Ha-, Ki-, and N-ras genes.

Mutation or overexpression of certain host genes, including c-myc, Ha-ras, and Ki-ras, have been associated with genital squamous neoplasia, specifically in the cervix, and have been implicated in the natural history of these tumors. The relationship of these host gene alterations to vulvar squamous cell carcinomas has not been previously studied. We analyzed archival material from 13 human papillomavirus-positive and -negative vulvar squamous cell carcinomas for mutations in Ha-, Ki-, and N-ras genes, and a smaller number of fresh samples for c-myc amplification, using PCR-based assays. For comparison, eight cervical squamous cell carcinomas (three fixed and five fresh) were also analyzed. Analysis for ras mutations revealed a previously reported silent allelic variant at nucleotide 1744 in the Ha-ras gene, but no mutations in codons 12, 13, or 61. Similarly, genomic amplification of c-myc beyond a maximum of three haploid copies was not identified in the cases. These findings indicate that alterations in myc or ras sequences are not linked to vulvar squamous cell carcinomas or to the presence or absence of HPV nucleic acids. Moreover, they apparently will not distinguish vulvar from cervical carcinomas, both groups appearing to be unlikely to harbor these sequence alterations.

Base Sequence

Case report: rectal stenosis due to extramedullary haemopoiesis--radiological features.

Although extramedullary haemopoiesis (EMH) is relatively common in myelofibrosis, it is seldom symptomatic and rarely involves the intestinal tract. We report a case in which perirectal infiltrate resulted in clinically symptomatic constipation. The barium enema showed tubular rectal narrowing with mucosal pleating. On computed tomography a poorly marginated soft tissue mass was shown to be replacing the perirectal fat.

Aged

Comparison between sonographic morphology and Doppler waveform for the diagnosis of ovarian malignancy.

OBJECTIVE: To assess the accuracy of pelvic sonography in distinguishing benign from malignant lesions in postmenopausal women, using morphologic criteria and Doppler flow characteristics. METHODS: All postmenopausal patients scanned from March 1992 to April 1993 with sonographically identified and pathologically confirmed adnexal masses formed the study group. The adnexal lesions were morphologically categorized prospectively as benign or malignant, and pulsed Doppler flow studies were measured using the lowest resistance index obtained from each mass. The sensitivity and specificity were determined for morphologic and Doppler flow assessments, as well as for a combination of these methods, for predicting the presence of malignancy. RESULTS: Thirty-three postmenopausal patients formed the study group; 12 lesions were malignant and 21 were benign pathologically. Using morphologic criteria alone, the sensitivity in detecting malignancy was 91% and specificity was 52%. Using pulsed Doppler alone with a resistance index limit of 0.6, the sensitivity in predicting malignancy was 66%, with a specificity of 81%. If a resistance index limit of 0.8 were used, the sensitivity and specificity would be the same as those for morphology alone. Combining morphology and resistance index, a single malignancy would still have been missed (sensitivity 91%). CONCLUSION: In our experience, Doppler flow studies did not add substantially to the prediction of malignancy using morphologic assessment alone.

Diagnosis, Differential

Use of peripheral-blood progenitor cells abrogates the myelotoxicity of repetitive outpatient high-dose carboplatin and cyclophosphamide chemotherapy.

PURPOSE: Attempts to increase dose-intensity in clinical practice have been limited by cumulative hematologic toxicity despite the use of hematopoietic growth factors. To address this problem, we designed a study to determine whether four cycles of dose-intensive chemotherapy with carboplatin could be administered in the outpatient setting using granulocyte-macrophage colony-stimulating factor (GM-CSF) and peripheral-blood progenitor cells (PBPCs) that had been harvested before initiation of treatment. PATIENTS AND METHODS: An initial cycle (cycle no. 0) of cyclophosphamide 4 g/m2 followed by GM-CSF was used to mobilize PBPCs harvested by leukapheresis for 6 consecutive days. Cycles no. 1 through 4 consisted of outpatient carboplatin 600 mg/m2 and cyclophosphamide 600 mg/m2 followed by GM-CSF 5 micrograms/kg subcutaneously (SC) twice per day every 28 days. In cycle no. 1, PBPC were not reinfused to assess the effects of GM-CSF alone. In cycles no. 2 through 4, PBPCs were reinfused on day 3 in an outpatient setting. RESULTS: In eight assessable patients, the addition of PBPCs in cycle no. 2 resulted in a significant reduction in the median duration of thrombocytopenia less than 20,000/microL (6.5 v 1 day; P = .016), days to platelets more than 50,000/microL (20.5 v 15 days; P = .020), number of platelet transfusions (five v 1.5; P = .016), and duration of neutropenia (absolute neutrophil count [ANC] < 1,000/microL (7 v 2.5 days; P = .008) when compared with cycle no. 1. Dose-limiting hematologic toxicity, defined as more than 7 days of platelets less than 20,000/microL or ANC less than 500/microL, was observed in four of eight patients during cycle no. 1, but not during cycles no. 2, 3, and 4 of chemotherapy supported by PBPCs (a total of 19 cycles in eight patients). Five of eight patients completed all four cycles of high-dose therapy. Three patients did not complete four cycles due to late thrombocytopenia (n = 2) or tumor progression (n = 1). CONCLUSION: These results indicate a benefit of PBPCs in addition to GM-CSF in alleviating myelosuppression of dose-intensive chemotherapy. Initial collection of PBPCs may allow administration of repetitive cycles of high-dose chemotherapy with acceptable toxicity to outpatients at disease onset.

Adult

Double gloving. Protecting surgeons from blood contamination in the operating room.

Health care workers, particularly surgeons, understand the importance of preventing contamination from blood of patients infected with deadly viruses. One of the most common areas of contamination is the hands and fingers due to the failure of glove protection. There are varying opinions regarding the frequency of glove failure, the necessity of wearing two gloves for added protection, and the ability to operate when wearing two gloves. We performed a prospective, randomized, trial of 143 procedures involving 284 persons to answer these questions for surgeons and first assistants. Overall, the glove failure rate (blood contamination of the fingers) was 51% when one glove was worn and 7% when two gloves were worn. Acceptability was 88% in the group who agreed to wear two gloves, and 88% of these did not perceive that tactile sense was significantly impaired. We believe that double gloving should be, and can be, used routinely during major surgical procedures to protect surgeons from blood contamination.

Blood

In-use evaluation of surgical gowns.

Surgical gowns must protect patients from the bacteria of operating room personnel and also protect staff members from the lethal viruses in the blood of patients. The current study was done to evaluate the barrier function of several surgical types of gowns during use in surgical procedures and identify the frequency of failure of the gowns and some causes for this failure. We performed direct observation of 234 operations during which the surgeon and the first assistant wore 535 gowns. Blood strikethrough occurred most often when contamination on the outside of the gown was heavy (20 per cent), but still occurred after medium (7 per cent) and small (1 per cent) contamination. We found significant differences between gowns based on the material used and the design of the gowns. Gowns reinforced with a second layer of material or a layer of plastic material were more effective at preventing strikethrough than a single layer of material. One gown was identified that was unacceptable for any use in the operating room. Gowns of different designs and degrees of protection should be chosen based on the body area likely to be exposed to blood and the amount of predicted blood contamination. Further improvement in gown materials and design are required, since surgeons cannot consider any of these gowns protective during strenuous use.

Blood

Well-differentiated hepatocellular carcinoma associated with long-term survival. Report of two cases.

Two cases of well-differentiated hepatocellular carcinoma (HCC) with focal biliary differentiation are presented. The distinct histological features of these neoplasms and the unusually protracted clinical course of 8 and 10 years distinguish them from previously described pathological categories of primary hepatic tumors. Electron microscopic and immunohistochemical findings support a dual hepatic and bile duct differentiation of the tumor cells. If additional examples of this tumor are found to be associated with a similarly prolonged symptom-free survival, the distinction of this entity from traditional, rapidly fatal HCC becomes important. Less aggressive therapeutic options may be entertained.

Adult

Risk of blood contamination and injury to operating room personnel.

The potential for transmission of deadly viral diseases to health care workers exists when contaminated blood is inoculated through injury or when blood comes in contact with nonintact skin. Operating room personnel are at particularly high risk for injury and blood contamination, but data on the specifics of which personnel are at greater risk and which practices change risk in this environment are almost nonexistent. To define these risk factors, experienced operating room nurses were employed solely to observe and record the injuries and blood contaminations that occurred during 234 operations involving 1763 personnel. Overall 118 of the operations (50%) resulted in at least one person becoming contaminated with blood. Cuts or needlestick injuries occurred in 15% of the operations. Several factors were found to significantly alter the risk of blood contamination or injury: surgical specialty, role of each person, duration of the procedure, amount of blood loss, number of needles used, and volume of irrigation fluid used. Risk calculations that use average values to include all personnel in the operating room or all operations performed substantially underestimate risk for surgeons and first assistants, who accounted for 81% of all body contamination and 65% of the injuries. The area of the body contaminated also changed with the surgical specialty. These data should help define more appropriate protection for individuals in the operating room and should allow refinements of practices and techniques to decrease injury.

Blood