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Biomedical subjects

R Jacobs

Publications and source records attributed to R Jacobs.

At least 91 records · Page 5Linked to original sources

Evaluation of the psychophysical detection threshold level for vibrotactile and pressure stimulation of prosthetic limbs using bone anchorage or soft tissue support.

In the present study the psychophysical detection threshold levels mechanical stimulation of 32 prosthetic limbs were determined. Prosthetic limbs were anchored to the bone by means of an implant (n=17) or supported by a socket enclosing the amputation stump (n=15). Detection threshold levels were assessed for pressure and vibratory stimulation of the prosthesis and the limb at the contralateral side (control). Following vibratory stimulation, thresholds were increased on an average 20% for socket prostheses. but approached those of the control for bone-anchored prostheses. For pressure stimulation, thresholds were increased up to 60% for socket prostheses and 40% for bone-anchored prostheses compared to the control. While bone-anchored prostheses yielded significantly lower threshold levels than socket prostheses, there was no significant difference between both treatments regarding pressure stimulation. Results were applicable to both upper and lower limb amputees. It could be concluded that detection thresholds for pressure and especially vibratory stimulation of prosthetic limbs were generally higher than for control limbs. The outcome was related to the prosthetic limb design with bone-anchored prostheses yielding better perception than socket prostheses.

Adult↗

Biologic outcome of single-implant restorations as tooth replacements: a long-term follow-up study.

BACKGROUND: The replacement of a single tooth or several teeth by means of single-implant restorations is an increasingly used method that needs long-term validation. PURPOSE: The goal of this study was to evaluate the outcome of single-implant restorations by means of fixed restorations and to define the prognosis through marginal bone level estimations. MATERIALS AND METHODS: From November 1986 to June 1998, 270 Brånemark implants (215 in the upper jaw) were installed in 219 patients (106 males). Both anterior and posterior sites were involved. Of the 263 single restorations, 28 were placed in private dental offices. The patients were followed until June 1999. RESULTS: Twelve implants failed before or at abutment connection or within 6 months afterward. Only four implants failed later. The cumulative success rates were 93% for the implants and 96.5% for the restorations over a period of 11 years. The marginal bone loss during the first 6 months after abutment connection reached 0.71 mm and then dropped to 0.036 mm annually over a period of 10 years. CONCLUSIONS: Single-implant restorations (Brånemark System) are a reliable treatment with a good long-term prognosis. Failures were concentrated during the healing period and early loading phase.

Adolescent↗

Lymphocyte subsets and cellular immunity in patients with chronic pancreatitis.

BACKGROUND: An abnormal immune response may play a pathogenetic role in chronic pancreatitis. However, to date characterization of the systemic immunological changes in patients with chronic pancreatitis has not been undertaken. METHODS: Lymphocyte phenotypes and proliferation ((3)H-thymidine) after stimulation with mitogens and interleukin-2 were studied in peripheral mononuclear cells from 11 patients with chronic pancreatitis (alcohol-induced n = 6; idiopathic pancreatitis n = 5). The natural killer cell activity was investigated in a (51)Cr release cytotoxicity assay. In vitro cytokine release of stimulated mononuclear cells was measured. RESULTS: Flow cytometric studies showed a significant decrease in the percentage of circulating CD8+, CD56+ and CD25+ cells in patients with chronic pancreatitis independent of the etiology. Comparing all patients with chronic pancreatitis to controls, the proliferation rate was not significantly increased, but patients with pain (n = 5) showed increased proliferation in comparison to patients without pain (n = 6). No significant difference in natural killer cytotoxicity was observed. The in vitro release of tumor necrosis factor-alpha and interleukin-10 by stimulated mononuclear cells was increased. CONCLUSIONS: Chronic pancreatitis is accompanied by systemic immune dysregulation. The observed changes in peripheral mononuclear cells reveal additional evidence that the cell-mediated immune response may contribute to the development of pain and tissue destruction in chronic pancreatitis.

Adult↗

Antimicrobial selection for hospitalized patients with presumed community-acquired pneumonia: a survey of nonteaching US community hospitals.

OBJECTIVE: To describe and evaluate empiric antimicrobial regimens chosen for hospitalized patients with presumed community-acquired pneumonia (CAP) in US hospitals, including compliance with the American Thoracic Society (ATS) guidelines. Secondary outcomes included length of stay (LOS) and mortality associated with the choice of therapy. METHODS: A nonrandomized, prospective, observational study was performed in 72 nonteaching hospitals affiliated with a national group purchasing organization. Patients with an admission diagnosis of physician-presumed CAP and an X-ray taken within 72 hours of admission were eligible for the study. Demographic, antibiotic selection, and outcomes data were collected prospectively from patient charts. RESULTS: 3035 patients were enrolled; 2963 were eligible for analysis. Compliance with the ATS guidelines was 81% in patients with nonsevere CAP. The most common antibiotic regimen used for empiric treatment was ceftriaxone alone or in combination with a macrolide (42%). The overall mortality rate was 5.5%. The addition of a macrolide to either a second- or third-generation cephalosporin or a beta-lactam/beta-lactamase inhibitor was associated with decreased mortality and reduced LOS. CONCLUSIONS: Most hospitalized patients with CAP receive antimicrobial therapy consistent with the ATS guidelines. The addition of a macrolide may be associated with improved patient outcomes.

Adolescent↗

The UNC-119 family of neural proteins is functionally conserved between humans, Drosophila and C. elegans.

C. elegans animals mutant for the unc-119 gene exhibit movement, sensory and behavioral abnormalities. Consistent with a nervous system role, unc-119 reporter genes are expressed throughout the C. elegans nervous system. The UNC-119 protein has strong sequence similarity to the predicted protein from a human gene, HRG4/HsUNC-119, whose transcript is abundant in the retina. Using these similarities, we have identified a Drosphila homolog, DmUNC-119, which is expressed in the Drosophila nervous system. The predicted C. elegans, human and Drosophila gene products are conserved across two domains. Expression of portions of HRG4/HsUNC-119 or DmUNC-119, directed by the unc-119 promoter, can fully rescue the C. elegans unc-119 mutant phenotype. We tested the ability of portions of HRG4/HsUNC-119 to rescue, and found that its function in C. elegans requires the conserved carboxyl terminus, while the dissimilar amino terminus is dispensable. UNC-119, HRG4 and DmUNC-119 constitute members of a new class of neural genes whose common function has been maintained through metazoan evolution.

Adaptor Proteins, Signal Transducing↗

[Bruxism and overload of periodontium and implants].

Bruxism is responsible for occlusal tooth wear but can not induce nor aggravate gingivitis or periodontitis. Bruxism induces jiggling forces, which cause a clinical tooth hypermobility, radiologically seen as a widened periodontal space. Although there is no direct causal relation between bruxism and implant failure, implant overload may lead to fractures of the components and bone loss.

Bruxism↗

Immunologic and virologic studies in long-term nonprogressors with HIV-1 infection.

BACKGROUND: It is not known whether clinical latency in long-term nonprogressors (LTNP) with HIV-1 infection is due to a strong HIV-1 specific immune response of the host or to virologic factors. - METHODS: Peripheral blood mononuclear cells (PBMC) of 6 LTNP were analyzed for their phenotype, proliferation rates, natural killer (NK) cell activity, antibody dependent cellular cytotoxicity (ADCC), and CCR5 chemokine receptor genotype. Furthermore sequence analyses of the HIV-1 gene were performed. - RESULTS: Phenotypic analyses of lymphocyte subsets revealed increased CD8+ as well as HLA-DR+ expressing cells in LTNP and patients with progressive disease (PRO). Proliferation assays in LTNP and PRO showed a reduction of stimulation by polyclonal mitogens (PHA, ConA, PWM) of up to 60%. NK activity was within normal ranges in LTNP but reduced in PRO. 1 LTNP exhibited heterozygosity for CCR5-D32. A mutant HIV nef gene was not discovered by PCR in any of the LTNP. HIV-V3 loop PCR in 5 LTNP revealed the HIV-1B (NSI) subtype. In 2 patients further sequence analyses of the HIV-1 genome showed homozygous mutations in the Sp1 and NF-kB binding sites. CONCLUSION: The non-progression of HIV-1 infection in some LTNP seems to be due to single mutations in the viral genome resulting in a less replicative HIV-1 subtype or to a mutant chemokine receptor leading to a reduced HIV-1 entry into CD4+ cells. NK cell activity might be an additional contributing factor in controlling viremia.

Acquired Immunodeficiency Syndrome↗

Results of a phase II concurrent chemoradiotherapy study using three-dimensional conformal radiotherapy with cisplatin and oral etoposide in stage III nonsmall-cell lung cancer.

This phase II study was designed to utilize conformal radiation therapy with cisplatin and oral etoposide in patients with stage III or locally recurrent non-small-cell lung cancer to determine tolerance and toxicity of therapy. From April 1992-February 1996, 18 patients with pathologically confirmed stage IIIA, IIIB, or locally recurrent non-small-cell lung cancer (NSCLC) were entered on study. Metastatic workup included a CT scan of the thorax and upper abdomen as well as a bone scan. Chemotherapy consisted of IV cisplatin (100 mg/m2) with IV etoposide (25 mg/m2) on day 1; oral etoposide was given (50 mg/m2) days 2-14. Using three-dimensional planning, 40-45 Gy were delivered to the clinical target volume, followed by a boost to the gross tumor volume for a total of 70 Gy. Patients with recurrent disease received 40-50 Gy in total. Eighteen patients were enrolled: 16 patients were treated with curative intent and were evaluable for outcome. Two patients were treated for locally recurrent NSCLC and were not included in the outcome analysis. Stages included IIIA (44%) and stage IIIB (54%). Forty-four percent had T3/4 tumors, and 69% had N2/3 disease. Overall survival at 1 year was 64%, while 2-year overall survival was 50%. Distant metastasis-free survival at 1 year was 67%, and at 2 years 60%. The 1-year chest progression-free survival was 57%, and at 2 years 50%. Sixty-three percent required hospitalization for dehydration or neutropenia. Fifty-six percent developed leukopenia (<1,000 cells/microl) sometime during the therapy. We conclude that concurrent cisplatin and oral etoposide with conformal radiation therapy provide encouraging results in stage III lung cancer. The major toxicities of this therapy included leukopenia, thrombocytopenia, and mucosal esophagitis. Local progression of disease continues to be a problem with the current doses given. Future studies should evaluate dose escalation of radiation therapy with limited volumes, utilizing conformal radiation and chemotherapy to improve local control and potentially impact upon distant metastases.

Administration, Oral↗

Patients with systemic lupus erythematosus differ from healthy controls in their immunological response to acute psychological stress.

Clinical observations suggest that psychological stress induces exacerbation of disease activity in patients with systemic lupus erythematosus (SLE). In order to determine whether SLE patients differ from healthy controls in their stress response, we analyzed heart rate, blood pressure, catecholamine concentration, lymphocyte subpopulations, natural killer (NK) cell activity, and expression of beta-adrenoceptors on PBMC before, immediately after, and 1 h after a public speaking task in 15 SLE patients and 15 healthy subjects. Both groups demonstrated similar psychological, cardiovascular, and neuroendocrine responses to acute stress. However, natural killer (CD16(+)/CD56(+)) cell numbers transiently increased after stress exposure, with significantly less pronounced changes in SLE patients. In addition, NK activity increased in healthy controls (n = 8) but not in SLE patients (n = 4) after acute stress. Furthermore, the number of beta(2)-adrenoceptors on PBMC significantly increased only in healthy subjects (n = 8) after stress but not in SLE patients (n = 7). These data indicate that SLE patients differ from healthy controls in stress-induced immune responses.

Acute Disease↗

A multisensory integration model of human stance control.

A model is presented to study and quantify the contribution of all available sensory information to human standing based on optimal estimation theory. In the model, delayed sensory information is integrated in such a way that a best estimate of body orientation is obtained. The model approach agrees with the present theory of the goal of human balance control. The model is not based on purely inverted pendulum body dynamics, but rather on a three-link segment model of a standing human on a movable support base. In addition, the model is non-linear and explicitly addresses the problem of multisensory integration and neural time delays. A predictive element is included in the controller to compensate for time delays, necessary to maintain erect body orientation. Model results of sensory perturbations on total body sway closely resemble experimental results. Despite internal and external perturbations, the controller is able to stabilise the model of an inherently unstable standing human with neural time delays of 100 ms. It is concluded, that the model is capable of studying and quantifying multisensory integration in human stance control. We aim to apply the model in (1) the design and development of prostheses and orthoses and (2) the diagnosis of neurological balance disorders.

Afferent Pathways↗

Absence of the alpha6(IV) chain of collagen type IV in Alport syndrome is related to a failure at the protein assembly level and does not result in diffuse leiomyomatosis.

X-linked Alport syndrome is a progressive nephropathy associated with mutations in the COL4A5 gene. The kidney usually lacks the alpha3-alpha6 chains of collagen type IV, although each is coded by a separate gene. The molecular basis for this loss remains unclear. In canine X-linked hereditary nephritis, a model for X-linked Alport syndrome, a COL4A5 mutation results in reduced mRNA levels for the alpha3, alpha4, and alpha5 chains in the kidney, implying a mechanism coordinating the production of these 3 chains. To examine whether production of alpha6 chain is under the same control, we studied smooth muscle cells from this animal model. We determined the canine COL4A5 and COL4A6 genes are separated by 435 bp, with two first exons for COL4A6 separated by 978 bp. These two regions are >/= 78% identical to the human sequences that have promoter activity. Despite this potential basis for coordinated transcription of the COL4A5 and COL4A6 genes, the alpha6 mRNA level remained normal in affected male dog smooth muscle while the alpha5 mRNA level was markedly reduced. However, both alpha5 and alpha6 chains were absent at the protein level. Our results suggest that production of the alpha6 chain is under a control mechanism separate from that coordinating the alpha3-alpha5 chains and that the lack of the alpha6 chain in Alport syndrome is related to a failure at the protein assembly level, raising the possibility that the alpha5 and alpha6 chains are present in the same network. The lack of the alpha6 chain does not obviously result in disease, in particular leiomyomatosis, as is seen in Alport patients with deletions involving the COL4A5 and COL4A6 genes.

Animals↗

Long-term efficacy of treatment of chronic hepatitis C with alpha interferon or alpha interferon and ribavirin.

The major objective of treatment of chronic hepatitis C virus (HCV) infection is to prevent progression to cirrhosis, and thereby prevent complications of end-stage liver disease. The established treatment of chronic HCV is with alpha interferon. Recent results with ribavirin and alpha interferon together suggest that combination antiviral therapy will become the benchmark treatment. For both naive and relapsed patients, however, it has become important to assess the long-term outcome of treatment, in order to gauge whether treatment has indeed modified the natural history of chronic hepatitis C virus infection. It seems likely that most sustained responders (85-90%) treated with combination ribavirin and alpha interferon will continue to have a long-term biochemical and virological response, as has been demonstrated with alpha interferon alone, but further long-term follow-up of patients treated with combination therapy is required.

Antiviral Agents↗

Effects of fentanyl on cellular immune functions in man.

In order to analyze the effects of the opioid agonist fentanyl on cells of the innate immune system, seven healthy individuals were treated intravenously with the opioid fentanyl and five subjects received a placebo. Respiratory burst of polymorphonuclear cells (PMNC) and phenotypes of peripheral blood lymphocytes (PBL) were analyzed from blood samples drawn before, 15 and 30 min after fentanyl or placebo application. In addition, in vitro effects of fentanyl on natural killer (NK) activity was assessed. Fentanyl administration affected neither superoxide production of PMNC nor circulating numbers of B-and T-lymphocytes. In contrast, NK cell (CD16+/CD56+) numbers significantly increased in response to fentanyl. However, no direct influence of fentanyl on NK cell function in vitro could be detected. These results suggest a transient effect of fentanyl on NK cell circulation which seemed to be centrally mediated rather than a direct effect of this opioid on NK cells.

Adult↗

Predictability of reformatted computed tomography for pre-operative planning of endosseous implants.

OBJECTIVES: To determine the reliability of reformatted 2D-CT for pre-operative planning of implant placement. METHODS: One hundred consecutive partially or fully edentate patients underwent 2-D reformatted CT pre-operative planning and subsequent implant placement. The number, site and size of the implants, the available bone height and anatomical complications were recorded. The pre-operative planning and the outcome at surgery were compared statistically using a percentage agreement and Kendall's correlation coefficient. RESULTS: Agreement between the pre- and intra-operative data was good for the number of implants (60%) and the selected sites (70%). From a total of 416 implants planned, 21 implants could not be placed because of intra-operative findings. Agreement was relatively poor for implant size (44%) and anatomical complications (46%). Kendall's correlation coefficient was highest for the number of implants (0.80) and implant sites (0.81). It was much lower for implant sizes (0.51) and did not reach significance for anatomical complications (0.09). CONCLUSIONS: Reformatted 2D-CT is reliable for the pre-operative assessment of the number and sites of implants in the jaws. It is less predictable for the implant size needed and poor for anatomical complications.

Adolescent↗

Predictability of a three-dimensional planning system for oral implant surgery.

OBJECTIVES: To compare 2D CT alone with 2D + 3D reconstruction for pre-operative planning of implant placement. METHODS: Spiral CT scans of 33 consecutive patients were used for both reformatted 2D and 3D computer-assisted planning. The number, site and size of implants and the occurrence of anatomical complications during planning and implant placement were statistically compared using the percentage agreement and the Kendall's correlation coefficients (tau). Although planning was performed in 33 patients, implants were only placed in 21 patients. In 11 patients surgery was based on 2D + 3D imaging and in ten patients on 2D planning. RESULTS: Agreement between planning and placement of implants was highly significant for the implant sites selected. For 2D based planning and placement, agreement reached 68% (tau = 0.94). For 2D + 3D based planning and placement, agreement attained 73% (tau = 0.89). For planning and placement of implant size based on 2D images, agreement was 31% and not significant (tau = 0.23). When based on 2D + 3D images, agreement for implant size was 44% (tau = 0.5). Agreement was not significant for anatomical complications: 69% for 2D planning and 71% for 2D + 3D planning (tau = 0.24 for 2D and tau = 0.21 for 2D + 3D). CONCLUSIONS: The 3D planning system is a reliable tool for pre-operative assessment of implant placement. Both 2D and 2D + 3D planning have a good predictability for the number and site of the implants but less so for anatomical complications. However, the 2D + 3D planning provides a better pre-operative assessment of implant size.

Adult↗

Clinical presentation of tuberculosis in culture-positive children. Pediatric Tuberculosis Consortium.

BACKGROUND: Because tuberculosis (TB) in children implies recent infection, children serve as sentinels for disease transmission within a community. Despite the significance of diagnosing tuberculosis in children, most cases are diagnosed on clinical evidence rather than laboratory findings. METHODS: We analyzed the demographic and clinical presentation of 156 children with culture proven tuberculosis using Epi-Info Version 6. RESULTS: Although the clinical characteristics of this population were generally consistent with those seen in previous studies, several unexpected results were observed. Boys were overrepresented in the group of very young children (72% < 1 year). Many of the children had coexisting diseases not known to predispose to TB (37%). Cavitation, usually observed in older children, was seen in four children < or = 1 year of age. Few children were homeless or HIV-infected, but many (42%) lived in female-headed households. Of the adult contacts at risk for TB, many (49%) were recent immigrants to the US. Overall 34% of the population was either foreign born or the children of recent immigrants. CONCLUSIONS: This series of 156 culture-positive children provides an understanding of the risk factors and clinical presentation of pediatric tuberculosis. The data emphasize the impact of the child's environment on the risk for tuberculosis.

Adolescent↗

Effects of fentanyl and low doses of alcohol on neuropsychological performance in healthy subjects.

The effects of the opioid fentanyl and low doses of alcohol on neuropsychological functions in healthy volunteers were measured. Twenty-four healthy male volunteers participated in this study. Two randomised placebo-controlled cross-over trials were conducted. In group 1, 6 subjects received fentanyl (0.2 microgram/kg body weight) in the order of fentanyl/placebo and 6 subjects in the order of placebo/fentanyl. Group 2 received alcohol in a similar procedure by continuous intravenous infusion, leading to a blood alcohol concentration (BAC) of 0.03%. Impairment was measured via different neuropsychological tests. The results indicate that fentanyl in concentrations commonly used in out-patient surgical procedures produces pronounced cognitive impairment (auditory reaction time, signal detection, sustained attention, recognition) in comparison to placebo. After application of low doses of alcohol (BAC 0.03%) only visual reaction time was impaired in comparison to placebo.

Adult↗