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Biomedical subjects

D Cummings

Publications and source records attributed to D Cummings.

At least 19 recordsLinked to original sources
PubMed2006

Changes in 24-h area-under-the-curve ghrelin values following diet-induced weight loss are associated with loss of fat-free mass, but not with changes in fat mass, insulin levels or insulin sensitivity.

OBJECTIVE: To determine which parameters of body composition or metabolism best correlate with changes in 24 h ghrelin levels following weight loss. DESIGN: A 3-month low-calorie diet followed by 3 months of weight stabilization. SUBJECTS: Twelve overweight and obese adult men and women. MEASUREMENTS: Body composition by underwater weighing, abdominal fat depots, leptin, ghrelin and parameters of insulin and lipid metabolism. RESULTS: Increased 24 h ghrelin levels after weight loss correlated with decreases in body mass index, subcutaneous fat and fat-free mass (FFM), but not with changes in fat mass, fat cell size, leptin, insulin, insulin sensitivity, lipids or free fatty acid levels. The change in FFM correlated with the rise in ghrelin levels independently of body adiposity. DISCUSSION: Alterations in FFM with diet-induced weight loss may play a role in ghrelin regulation. Changes in ghrelin levels could, then, serve as an integrative signal reflecting changes in FFM to hypothalamic centers controlling energy homeostasis.

Adipose Tissue↗
PubMed2000

Characterization of the binding site on the formyl peptide receptor using three receptor mutants and analogs of Met-Leu-Phe and Met-Met-Trp-Leu-Leu.

The formyl peptide receptor (FPR) is a chemotactic G protein-coupled receptor found on the surface of phagocytes. We have previously shown that the formyl peptide binding site maps to the membrane-spanning region (Miettinen, H. M., Mills, J. S., Gripentrog, J. M., Dratz, E. A., Granger, B. L., and Jesaitis, A. J. (1997) J. Immunol. 159, 4045-4054). Recent reports have indicated that non-formylated peptides, such as MMWLL can also activate this receptor (Chen, J., Bernstein, H. S., Chen, M., Wang, L., Ishi, M., Turck, C. W., and Coughlin, S. R. (1995) J. Biol. Chem. 270, 23398-23401.) Here we show that the selectivity for the binding of different NH(2)-terminal analogs of MMWLL or MLF can be markedly altered by mutating Asp-106 to asparagine or Arg-201 to alanine. Both D106N and R201A produced a similar change in ligand specificity, including an enhanced ability to bind the HIV-1 peptide DP178. In contrast, the mutation R205A exhibited altered specificity at the COOH terminus of fMLF, with R205A binding fMLF-O-butyl > fMLF-O-methyl > fMLF, whereas wt FPR bound fMLF > fMLF-O-methyl approximately fMLF-O-butyl. These data, taken together with our previous finding that the leucine side chain of fMLF is probably bound to FPR near FPR (93)VRK(95) (Mills, J. S., Miettinen, H. M., Barnidge, D., Vlases, M. J., Wimer-Mackin, S., Dratz, E. A., and Jesaitis, A. J. (1998) J. Biol. Chem. 273, 10428-10435.), indicate that the most likely positioning of fMLF in the binding pocket of FPR is approximately parallel to the fifth transmembrane helix with the formamide group of fMLF hydrogen-bonded to both Asp-106 and Arg-201, the leucine side chain pointing toward the second transmembrane region, and the COOH-terminal carboxyl group of fMLF ion-paired with Arg-205.

Alanine↗
PubMed1999

Development and use of a 293 cell line expressing lac repressor for the rescue of recombinant adenoviruses expressing high levels of rabies virus glycoprotein.

An expression cassette designed for high-level production of rabies virus glycoprotein (RG) could not be rescued into a replication-defective, adenovirus-based vector using standard procedures. To overcome this difficulty, a 293-based cell line, designated 293LAP13, was constructed that contained and expressed a derivative of the lac repressor protein. The lac operator sequence, to which the repressor binds, was incorporated into an expression cassette, containing a promoter and intron, designed for high-level production of RG. Insertion of a single operator sequence immediately downstream of the transcription start site and the use of the 293LAP13 cell line allowed recombinant viruses that could not be isolated with 293 cells to be rescued efficiently. The operator-containing virus reached higher titres in 293LAP13 than in parental 293 cells and also produced plaques more efficiently in 293LAP13 cells. Moreover, in non-complementing human and canine cell lines, adenovirus vectors with a promoter-intron expression cassette expressed RG at much higher levels than vectors lacking the intron. These observations, together with the demonstration that expression of RG by operator-containing vectors was repressed markedly in 293LAP13 cells and that this inhibition was relieved at least partly by IPTG, suggest that the 293LAP13 cell line may be useful for the rescue and propagation of many vectors in which high expression of the desired protein prevents vector rescue in 293 cells.

Adenoviruses, Human↗
PubMed1999

Syme amputation for the treatment of fibular deficiency. An evaluation of long-term physical and psychological functional status.

BACKGROUND: Syme amputation is an accepted treatment for fibular deficiency. With improvement in limb-lengthening procedures, there has been renewed interest in limb salvage for these patients. The purpose of the present study was to evaluate the physical and psychological results in ten young adults who had had a Syme amputation for the treatment of fibular deficiency when they were children. METHODS: The evaluation consisted of physical examination, prosthetic assessment, psychological testing, and physical performance testing of knee extension and flexion with use of a Cybex-II dynamometer. RESULTS: Five patients reported no difficulty with the involved limb since the Syme amputation, four had had minor secondary procedures (three medial distal femoral or proximal tibial hemiepiphyseodeses, one reconstruction with an autologous patellar ligament graft, one revision of the stump, and one tibial osteotomy) on the affected extremity, and one had mild instability of the knee that had been treated nonoperatively. All ten patients had an appropriate, functional Syme prosthesis, and none reported difficulty with walking or running. On psychological testing, this group generally did not differ from the norm with regard to occupational satisfaction, personal growth, relationships with family members and peers, and recreational behavior. The patients' overall assessment of self-reported quality of life and self-esteem was similar to that of normative adult samples. In general, these patients were leading active, productive lives and had always done so. CONCLUSIONS: On the basis of the results of this study, we concluded that young adults who have had a Syme amputation apparently are not limited in their ability to pursue and achieve personal goals. In order to justify recommending limb salvage rather than early Syme amputation for the treatment of fibular deficiency, the results of multistaged lengthening and reconstruction would have to match the functional, psychological, and cost-effective results for the patients whom we studied, who had had a Syme amputation.

Adolescent↗
PubMed1998

Computerized polymorphic marker identification: experimental validation and a predicted human polymorphism catalog.

A computational system for the prediction of polymorphic loci directly and efficiently from human genomic sequence was developed and verified. A suite of programs, collectively called POMPOUS (polymorphic marker prediction of ubiquitous simple sequences) detects tandem repeats ranging from dinucleotides up to 250 mers, scores them according to predicted level of polymorphism, and designs appropriate flanking primers for PCR amplification. This approach was validated on an approximately 750-kilobase region of human chromosome 3p21.3, involved in lung and breast carcinoma homozygous deletions. Target DNA from 36 paired B lymphoblastoid and lung cancer lines was amplified and allelotyped for 33 loci predicted by POMPOUS to be variable in repeat size. We found that among those 36 predominately Caucasian individuals 22 of the 33 (67%) predicted loci were polymorphic with an average heterozygosity of 0.42. Allele loss in this region was found in 27/36 (75%) of the tumor lines using these markers. POMPOUS provides the genetic researcher with an additional tool for the rapid and efficient identification of polymorphic markers, and through a World Wide Web site, investigators can use POMPOUS to identify polymorphic markers for their research. A catalog of 13,261 potential polymorphic markers and associated primer sets has been created from the analysis of 141,779,504 base pairs of human genomic sequence in GenBank. This data is available on our Web site (pompous.swmed.edu) and will be updated periodically as GenBank is expanded and algorithm accuracy is improved.

Computer Communication Networks↗
PubMed1998

Rhenium-188(Sn)HEDP for treatment of osseous metastases.

UNLABELLED: Rhenium-188 (tin) hydroxyethylidine diphosphonate [188Re(Sn)HEDP] is a new radiopharmaceutical that localizes in skeletal metastases and emits beta particles that may be therapeutically beneficial. METHODS: It was evaluated by in vitro and in vivo testing in the laboratory, in animals and in humans using 188Re from a variety of sources. It may be produced by a desk-top method developed previously for 186Re(Sn)HEDP using 188Re produced through neutron irradiation of either enriched 187Re or naturally occurring rhenium targets or the use of a 188W/188Re generator. RESULTS: So long as the mass of rhenium in the 188Re-perrhenate to be processed into 188Re(Sn)HEDP is at least 100 microg, satisfactory radiochemical yields and purity may be obtained by all methods. The 188Re(Sn)HEDP has biodistribution and radiation dosimetry characteristics that are similar to those noted previously for 186Re(Sn)HEDP and appears to result in similar benefits and toxicities in patients with skeletal metastases. External radiation exposure monitoring indicates that, only 4 hr after a therapeutic administration of 1110 MBq (30 mCi) of 188Re(Sn)HEDP, average exposure rates at 1 meter from the patient would be only 0.5 mR/hr. CONCLUSION: Same-day, on-demand, outpatient therapy of disseminated skeletal metastases appears to be feasible with 188Re(Sn)HEDP.

Aged↗
PubMed1995

I-123 MIBG scintigraphy in adults. A report of clinical experience.

Thirty-one adult patients with clinical findings suggestive of pheochromocytoma were studied with I-123 MIBG. All patients had images obtained at 24 and 48 hours. Five patients had abnormal uptake proved to be because of I-123 MIBG avid tumors. The remaining 26 patients had no proven tumors and showed physiologic uptake in various organs. The 24-hour images were of high quality. In all cases, the 48-hour images contributed no significant additional information. Only in 1 patient did the 48-hour image add some certainty. Physiologic uptake was seen in the salivary glands, liver, G.I. tract, and urinary bladder in all patients (100%). Uptake was also observed in the lung and heart (90%), normal adrenal glands (32%), thyroid (29%), spleen (23%) uterus (13%), and neck muscles (6%). The authors' experience indicates that I-123 MIBG gives superior images compared to the previously used I-131 MIBG, that the optimum imaging time for adults is 18-24 hours, and that normal distribution patterns including uterine and neck muscle uptake should be familiar to physicians interpreting the studies.

3-Iodobenzylguanidine↗
PubMed1995

Integrated disability management: taking a coordinated approach to managing employee disabilities.

1. Disability management provides opportunities to control costs and improve employee benefits through three levels of prevention: primary prevention of disabilities (work and non-work related); secondary minimization of disability costs; and tertiary facilitation of rehabilitation and early return to work. 2. A totally integrated disability management program has many components, all of which must be effectively coordinated. Management of these components will result in lower disability related costs, increased employee productivity and job satisfaction, and less employee turnover. 3. All employees receive individualized services designed to assist them in returning to work and emphasizing their contributions to the company's overall dedication to global leadership, continuous growth, and success.

Persons with Disabilities↗
PubMed1993

Laparoscopic orchiectomy in a patient with complete androgen insensitivity.

Many procedures that were once approached exclusively through large abdominal incisions are now accomplished using operative laparoscopic techniques with shorter, less expensive hospital stays and significantly reduced convalescence. This report describes a laparoscopic orchiectomy in a patient with complete androgen insensitivity and discusses the indications for gonadectomy in phenotypic females with an XY karyotype.

Adult↗
PubMed1992

Radioiodine-131 therapy for well-differentiated thyroid cancer--a quantitative radiation dosimetric approach: outcome and validation in 85 patients.

For almost five decades, 131I treatment of thyroid cancer has been based empirically on administered activity rather than on actual radiation doses delivered. In 1983, we defined radiation dose thresholds for successful treatment. This report is concerned with the subsequent validation of those thresholds in 85 patients. The successful ablation of thyroid remnants occurred after a single initial 131I administration in 84% of inpatients and in 79% of outpatients when treatment was standardized to a radiation dose of at least 30,000 cGy (rad). Administered activities low enough to permit outpatient therapy could be used in 47% of the patients. Lymph node metastases were treated successfully in 74% of patients with a single administration of 131I calculated to deliver at least 8,500 cGy (rad). For athyrotic patients with nodal metastases only, success was achieved in 86% of patients at tumor doses of at least 14,000 cGy (rad). These success rates are equal to or better than those reported with empiric methods of 131I administration. The individualized treatment planning selectively allocates hospitalization and higher exposures to 131I to those patients who require them.

Adenocarcinoma↗
PubMed1990

Pharmacokinetics of oral zidovudine (azidothymidine) in patients with AIDS when administered with and without a high-fat meal.

Zidovudine is the only drug currently approved for the treatment of HIV infection. The present recommended doses found to be efficacious in patients with AIDS (200 mg every 4 h) achieve serum zidovudine concentrations greater than 0.267 micrograms/ml (1 mumol/l). Since patients often take zidovudine with food, we have investigated the effect of a liquid high-fat meal on the rate of absorption of zidovudine and on the peak serum concentration achieved. Eight patients received their usual dose of zidovudine (100 mg or 250 mg), with and without a liquid high-fat meal, on two separate study days, in a randomized crossover fashion. Blood and urine samples were collected over a 4-h period. In the absence of food, zidovudine is rapidly absorbed; the time to reach maximal serum concentration (Tmax) was 0.68 (+/- 0.25) h and the mean peak serum concentration (Cmax) achieved was 0.49 (+/- 0.3) micrograms/ml (dose normalized to 100 mg dose). In the presence of a high-fat meal, Tmax was significantly prolonged [1.95 (+/- 0.69) h; P less than 0.05] and the Cmax reduced [0.245 (+/- 0.12) micrograms/ml; P less than 0.05]. This demonstrates that to achieve maximal zidovudine serum concentrations, patients should take this medication on an empty stomach.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Delayed administration of tissue plasminogen activator reduces intra-abdominal abscess formation.

Previous studies demonstrated that intraperitoneal fibrinolysis using tissue plasminogen activator (t-PA) prevented intraabdominal abscess formation in a rat fibrin clot infection model when administered simultaneously with the infecting inoculum. To more closely mimic the clinical setting, the efficacy of delayed administration of t-PA on intra-abdominal abscess formation was examined. A delay of 2, 6, and 18 hours had no effect on the rate of abscess formation but did reduce abscess size, indicating partial fibrinolysis. Since fibrin clots dehydrate in vivo, we hypothesized that a higher concentration of t-PA might be necessary to effect complete abscess resolution. High-dose t-PA (0.1 mg/mL) prevented abscess formation following a 6-hour delay and reduced mean weight following an 18-hour delay. Since heparin sodium may prevent new fibrin deposition and enhance t-PA activity, it was combined with t-PA to investigate potential synergistic effects. Despite adequate anticoagulation with heparin, no synergy with t-PA could be documented. In addition, the combination of antibiotics with t-PA did not affect its efficacy in vivo. We demonstrate that delayed administration of t-PA is effective in preventing abscess formation and may have implications for the clinical setting where initial surgical intervention is usually delayed.

Abdomen↗
PubMed1988

Caring for the HIV-infected adult.

As the number of persons infected with human immunodeficiency virus (HIV) dramatically escalates over the next few years, health care providers will increasingly be involved in their care. A thorough understanding of the broad spectrum of infection, from asymptomatic seropositivity to AIDS-related complex and overt AIDS, will help prepare care providers for the challenges ahead. This article identifies the clinical manifestations of infection, provides management plans for common problems, and discusses psychological and social issues pertinent to the care of HIV-infected adults.

AIDS-Related Complex↗
PubMed1986

Nail-gun injuries. Accident, homicide, or suicide?

It may be difficult to distinguish industrial accidents from suicide attempts or even assaults or homicide. Nail guns are relatively new industrial tools that can produce severe or fatal injuries. The configuration of the nail on patients' radiographs after such injuries can be helpful in determining the cause of injury. Steel nails that are bent are due to a ricochet and thus indicate accidental injury. Straight-nail injuries to the co-workers of nail-gun users are most likely due to over-penetration of the substance being nailed or accidental mid-air firing; however, intentional injury cannot be ruled out. Extremity injuries caused by straight steel nails in nail gun users are the result of carelessness or poor technique, but suicide should be considered when straight nails cause wounds to the chest, head, or abdomen.

Accidents, Occupational↗
PubMed1985

The significance of hydronephrosis after aortofemoral reconstruction.

Hydronephrosis due to ureteral obstruction is a rarely reported complication of aortic bypass grafting. Patients who had undergone aortic reconstruction were screened using serial real-time ultrasound examination to detect ureteral obstruction. The clinical course and incidence of graft complications, renal impairment, amputation, and death were determined for hydronephrotic patients and compared with the incidence of similar complications in a control group. Hydronephrotic patients had an extremely high incidence of graft infection, anastomotic aneurysm, graft thrombosis, and amputation. Obstructed ureters were at high risk for intraoperative injury during removal of infected aortic grafts. A subgroup of hydronephrotic patients who developed multiple anastomotic aneurysms without graft infection was identified. Hydronephrosis was frequently silent, and detection required active investigation. After aortic reconstruction, routine screening with real-time ultrasound examination appears warranted to identify a high-risk subset of patients.

Aged↗
PubMed1985

Percutaneous drainage of abscesses in the postoperative abdomen that is difficult to explore.

We have evaluated our experience with computerized tomography and ultrasonography guided percutaneous drainage of extrahepatic abdominal fluid collections in a group of 22 patients. The most common goal was to avoid or delay surgery on abdomens in which reoperation would be difficult, mainly in high-risk patients. Drainage of pancreatic fluid collections or abscesses was also attempted in a small number of the patients. Percutaneous drainage was curative in 69 percent of those with nonpancreatic abscesses but in only 33 percent of those with abscesses associated with the pancreas. There were no complications attributable to the procedure or to delays in subsequent surgical drainage. Two patients died from problems not directly related to the use of percutaneous drainage. Percutaneous catheter drainage of nonpancreatic abdominal abscesses can play a useful role in patients who are carefully selected because they possess a complex abdominal anatomy distorted by previous surgery and infection or they are at high risk if surgical exploration is carried out.

Abdomen↗