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Biomedical subjects

R Jacobs

Publications and source records attributed to R Jacobs.

At least 163 records · Page 9Linked to original sources

Linear single-dose pharmacokinetics of ganciclovir in newborns with congenital cytomegalovirus infections. NIAID Collaborative Antiviral Study Group.

The pharmacokinetic characteristics of ganciclovir were determined in neonates (age range, 2 to 49 days) after an 1-hour intravenous infusion of a single dose of either 4 mg/kg (n = 14) or 6 mg/kg (n = 13). Twenty-seven newborns with symptomatic cytomegalovirus inclusion disease were enrolled in this open phase I-II pharmacokinetics, safety, and tolerance trial of ganciclovir at one of two doses. Ganciclovir disposition was best described by a one-compartment open model with zero-order input and first-order elimination. The mean elimination half-life (t1/2) for both dose groups was 2.4 hours. The mean apparent volume of distribution (Vd) was 669 +/- 70 ml/kg for the 4 mg/kg group and 749 +/- 59 ml/kg for the 6 mg/kg group. The mean total body clearance (CL) for the 4 mg/kg and 6 mg/kg groups was 189 +/- 28 ml/hr/kg and 213 +/- 21 ml/hr/kg, respectively. No significant differences were observed in Vd or CL between the two groups. The Vd, expressed in milliliters, increased with increasing patient weight (r = 0.689; p = 0.0001). The CL, expressed in milliliters per hour per kilogram, increased with increasing age (r = 0.413; p = 0.032). No significant differences were observed between the two dose groups for the area under the curve normalized for dose (AUC/Dose) or the maximum plasma concentration normalized for dose (Cmax/Dose), indicating that ganciclovir exhibited linear pharmacokinetics in these neonates.

Creatinine↗

Comparison of clarithromycin and penicillin VK suspensions in the treatment of children with streptococcal pharyngitis and review of currently available alternative antibiotic therapies.

In a randomized investigator-blinded study, 506 children ages 6 months to 12 years with positive rapid direct antigen tests for Group A beta-hemolytic Streptococcus (GABHS) received treatment with either clarithromycin suspension, 7.5 mg/kg twice daily, or penicillin VK suspension, 13.3 mg/kg three times per day for 10 days. Signs and symptoms of pharyngitis or tonsillitis were evaluated and throat cultures were obtained before treatment, once during treatment and 4 to 6 days and 19 to 25 days posttreatment. All GABHS isolates were susceptible in vitro to clarithromycin. Successful clinical responses at the end of treatment were demonstrated in 169 of 176 (96%) evaluable clarithromycin-treated patients and 179 of 191 (94%) evaluable penicillin-treated patients. GABHS was successfully eradicated at end of treatment in 168 of 183 (92%) evaluable clarithromycin-treated patients compared with 162 of 199 (81%) evaluable penicillin-treated patients (P = 0.004). There were no significant changes in hematologic or serum chemistry parameters in either group. Both drugs were well-tolerated. The incidence and nature of adverse events were similar in the clarithromycin and penicillin groups, except for gastrointestinal complaints reported in 35 of 250 (14%) clarithromycin recipients compared with 12 of 256 (5%) penicillin recipients (P < or = 0.001). The results indicate that twice daily clarithromycin was as safe and effective as three times daily penicillin VK in the treatment of children with streptococcal pharyngitis or tonsillitis. Clarithromycin was statistically superior to penicillin VK in the eradication of GABHS.

Child↗

Chronic hepatic encephalopathy following portacaval shunt: management by loop ileostomy.

A 69 year old woman developed intractable episodic hepatic encephalopathy 12 years after an end-to-side portacaval shunt for variceal haemorrhage. Medical management was ineffective in preventing repeated episodes of encephalopathy and caused incapacitating faecal incontinence. A loop ileostomy was created with minimal morbidity and was effective in preventing further episodes of encephalopathy over a follow-up period of 33 months. The patient returned to a normal diet and was able to be discharged home from institutional care. Loop ileostomy is an alternative in the management of patients with hepatic encephalopathy who are poorly responsive to, and/or intolerant of, medical therapy following portasystemic shunt surgery.

Aged↗

Psychophysiological, neuroendocrine and cellular immune reactions under psychological stress.

Emotional stress is often followed by increased susceptibility to infections. Natural killer (NK) cells play a major role in the immediate immune response controlling this susceptibility. In this study on 45 first-time parachutists, it is demonstrated that highly controlled psychological stress increased psychophysiological variables, enhanced the secretion of sympathetic-adrenal hormones and also led to a significant increase of NK cells and their cytotoxic activity followed by a decrease below starting values. This immunological alteration is correlated with the secretion of noradrenaline during the emotional strain. Quick mobilization of these cytotoxic effector cells is suggested as a major mechanism for the effective adaptation of the immune system to stress situations.

Adult↗

Comparison between implant-supported prostheses and teeth regarding passive threshold level.

A passive threshold determination was carried out on 31 patients subdivided into four test groups according to different prosthesis types supported by osseointegrated implants. They were compared to a control group of 10 patients with nonrestored natural test teeth. Forces were generated by a solenoid-driven stimulating device, which was placed in contact with the implant or tooth prior to the actual force rise to avoid impact forces. The findings indicate that the threshold level of implants is 50 times higher than that of natural teeth when tapping is avoided, which might otherwise trigger distant receptors. Bone deformation triggering the periosteal mechanoreceptors is the most logical explanation for the sensation reported.

Adult↗

Healing of foot ulcers in immunosuppressed renal transplant patients.

Sixteen renal transplant patients were retrospectively studied to determine the time foot ulcerations healed. All patients were taking imuran and medrol. More recently, patients were also on cyclosporine. All were insulin-dependent diabetics. A control group was established from a pool of randomly selected, age-matched, insulin-dependent diabetics who were also observed for foot ulcerations. All treatment was given by one physician. Pulse volume recordings were obtained in all but eight patients, who were clinically believed to have normal vascular supply to the affected extremity. No statistically significant difference was found between these groups in this regard. Cultures were obtained in all patients when indicated; appropriate antibiotics were started. No major differences were noted with respect to infecting organism. The immunosuppressed group had no excellent results, and three good, 14 fair, and 23 poor results. The control group had ten excellent, 14 good, 11 fair, and 17 poor results. A higher failure rate may occur with limb-salvage surgery in the immunosuppressed patient. This observation confirms a long-held clinical suspicion.

Amputation, Surgical↗

Function of mono- and biarticular muscles in running.

In this study the function of leg muscles during stretch-shortening cycles in fast running (6 m.s-1) was investigated. For a single stance phase, kinematics, ground reaction forces, and EMG were recorded. First, rough estimates of muscle force, obtained by shifting the EMG curves +90 ms, were correlated with origin-to-insertion velocity (VOI). Second, active state and internal muscle behavior were estimated by using a muscle model that was applied for soleus and gastrocnemius. High correlations were found between estimates of muscle force and VOI time curves for mono-articular hip, knee, and ankle extensor muscles. The correlation coefficients for biarticular muscles were low. The model results showed that active state of gastrocnemius was high during increase of origin-to-insertion length (LOI), whereas active state of soleus was low during the start of increase of LOI and rose to a plateau at the time lengthening ended and shortening started. It seems that the difference in stimulation between gastrocnemius and soleus is a compromise between minimizing energy dissipation and using the stretch-shortening cycle optimally. Furthermore, it was found that the net plantar flexion moment during running reached a value of 302 Nm, which was 158% and 127% higher than the peak values reached in maximal jump and sprint push-offs, respectively. It was argued that the higher mechanical output in running than in jumping could be ascribed to the utilization of the stretch-shortening cycle in running. The higher values in running compared with sprinting, however, may lie in a difference in muscle stimulation.

Adult↗

Lennert's lymphoma presenting as prurigo nodularis.

Lennert's lymphoma is a peripheral T-cell lymphoma that only rarely involves the skin. We present the case of a forty-two-year-old man who experienced severe pruritus for ten months. He was repeatedly diagnosed as having neurodermatitis and prurigo nodularis before subtle hematologic clues suggested, and subsequent examination of bone and lymph node biopsy specimens confirmed, the diagnosis of Lennert's lymphoma. This report describes the case and presents a brief review of Lennert's lymphoma.

Adult↗

CD16- CD56+ natural killer cells after bone marrow transplantation.

Natural killer (NK) cells are phenotypically defined as lymphocytes expressing the antigens CD56 and mostly CD16 (Fc gamma RIII), but lacking CD3. A small CD3- CD16- CD56+ NK cell subset has been described in normal individuals representing less than 2% of peripheral blood lymphocytes. We analyzed here 70 patients for their reconstitution of the immune system during follow-up after autologous or allogeneic bone marrow transplantation. In 35% of these patients, two different NK cell subsets, namely CD56+dim and CD56+bright cells, were observed. The mean duration of these two subsets after transplant was 4 months. Sixty-five percent of the patients exhibited an increased number of NK cells, but only the typical CD16+ CD56+dim population. The CD56+bright subpopulation represented a particular CD3- CD16- NK subset, with posttransplant frequencies up to 70% of all NK cells and 40% of peripheral blood lymphocytes, respectively. In contrast to normal CD56+dim NK cells, CD56+bright cells coexpressed the activation antigens p75 beta-chain of interleukin-2 receptor (IL-2R), CD2R, and CD26, but were negative for CD16. NK and antibody-dependent cellular cytotoxicity activity of CD56+bright cells was low compared with CD56+dim NK cells. But using IL-2 and interferon gamma, their cytotoxicity could be enhanced even more than in CD56+dim lymphocytes. These different subsets may reflect distinct activation or differentiation steps of NK cells during reconstitution of the immune system. Their differential response to IL-2 may be of functional importance for posttransplant cytokine therapy.

Adult↗

Production of anti-NC1 antibody by affected male dogs with X-linked hereditary nephritis: a probe for assessing the NC1 domain of collagen type IV in dogs and humans with hereditary nephritis.

Some patients with hereditary nephritis (HN) who have received a renal transplant have been shown to form antibody with specificity for the NC1 domain of collagen type IV, a major constituent of glomerular basement membranes (GBM). We attempted to duplicate this phenomenon in a family of dogs with X-linked HN, a model for human X-linked HN, by immunizing affected male dogs with normal dog NC1 domain. A collagenase digest was prepared from normal dog GBM, the NC1 domain was separated into dimer (approximately 50 kDa) and monomer (24 kDa and 26 kDa) components by SDS-PAGE, and injected into two affected male dogs. Antisera obtained from both dogs contained antibody which reacted with the NC1 domain of dog and human GBM by a plate-binding radioimmunoassay, bound to the dimer and 26 kDa monomer bands by Western blotting, and staining dog and human GBM by immunofluorescence (IF). The affected male dog antiserum reacted equally by radioimmunoassay with the NC1 domain isolated from GBM of unaffected, affected male, and carrier female dogs in the family with X-linked HN, and bound by Western blotting to dimers and the 26 kDa monomer band of the NC1 domain of GBM in each group of dogs. However, the affected male dog antiserum differentiated these dogs by IF; it produced global staining of GBM of unaffected dogs, failed to stain GBM of affected male dogs, and produced segmental staining of GBM of carrier female dogs. Absorption of the affected male dog antiserum with normal dog NC1 domain eliminated the staining of dog GBM by IF, whereas staining persisted after absorption with affected male dog NC1 domain. The abnormal staining patterns of GBM seen by IF in the affected male and carrier female dogs and the results of the absorption studies imply an abnormality of one or more determinants in the 26 kDa monomer band of the NC1 domain of their GBM. Amino acid sequencing of this band identified the alpha 1(IV) chain of collagen type IV, a finding that has implications for the pathogenesis of canine X-linked HN. Absent and segmental staining respectively were also seen by IF in GBM of a male and female patient with HN, using the affected male dog antiserum. Thus, the results obtained in affected male and carrier female dogs with X-linked HN may also be relevant to patients with this disease.

Amino Acid Sequence↗

The importance of visual feedback on the accuracy of jaw and finger positioning in man.

The anatomical position of the mandible means that direct visual feedback is not possible. To clarify the role of visual information, several jaw- and finger-positioning tasks were designed, both in a 'free-movement' and an 'isolated' (arm or head fixed) state, with or without a visual feedback display of the target position. The subjects had to position the mandible or the index finger of the preferred hand on to a movable metal bar and to maintain a defined position coinciding with the target level provided on an oscilloscope screen. The position signal was tape recorded and computer analysed off-line. Digital filtering differentiated between the drift and the oscillations around the target (root mean square). The results demonstrated a lack of precision in the free-movement, finger-positioning task after withdrawal of visual feedback. For jaw opening and closing muscles, position control was less impaired when a visual feedback display was abolished. It was suggested that the efficiency of jaw positioning is not primarily determined by visual feedback.

Adult↗

Intermuscular coordination in a sprint push-off.

This study was designed to investigate the patterns of intermuscular coordination during a sprinting event. In previous research it was found that despite the indeterminacy problem of movement control, movements like vertical jumping, speed skating and cycling are performed in a stereotyped manner. It was hypothesized that this might be due to constraints associated with the transformation of joint rotations into the desired translation. The objective of the present study was to determine the extent to which the intermuscular coordination patterns during other movements also are performed in a stereotyped manner and, if that is true, whether this can be understood on the basis of such constraints. Seven elite sprint runners were instructed to execute an explosive sprinting dash. Ground reaction forces and cinematographic data were recorded for the second stance phase of the sprint. Simultaneously, electromyographic activity of nine leg muscles was recorded telemetrically. Linked-segment modeling was used to obtain net joint moments and net joint powers. Different athletes appeared to perform the sprint in a stereotyped manner. The muscle coordination pattern is characterized by a proximo to distal sequence in timing of the monoarticular muscles. When compared to the sequential pattern found in jumping, the biarticular hamstrings and rectus femoris muscles behave differently; in the sprint a more pronounced reciprocal activity between these muscles exists. The resulting movement pattern is characterized by a sequence of upper leg extension and plantar flexion. The observed sequence in timing of muscle activation patterns is aimed at solving the problems associated with the earlier identified geometrical and anatomical constraint. However, the coordination pattern cannot be fully understood on the basis of these constraints. A specific constraint is identified with respect to the direction of the ground reaction force, which explains the pronounced reciprocal activity of the biarticular hamstring and rectus femoris muscles. The intermuscular coordination pattern in the sprint can be seen as a compromise between the specific requirement of the sprint and the advantageous effect of a proximo to distal sequence as found previously for jumping.

Adult↗

Posterior jaw bone resorption in osseointegrated implant-supported overdentures.

For several years, osseointegrated implant-supported overdentures have been used in the rehabilitation of full edentulism with excellent results, at least in the lower jaw. This study involved 3 groups of patients with different prosthetic reconstructions: (1) mandibular overdentures supported by 2 implants connected by a bar (30 patients), (2) mandibular fixed prostheses supported by 4-6 implants (25 patients) and (3) mandibular complete dentures without implant support as controls (85 patients). The primary aim of this study was to examine on orthopantomograms (by means of the area index to minimize distortion and magnification errors), posterior mandibular ridge resorption in the 3 treatment groups. The present data demonstrated a minimal posterior mandibular ridge resorption in patients with fixed implant-supported prostheses. A more considerable posterior ridge resorption was observed in the complete denture group and especially in the overdenture wearers. For the latter, the annual posterior jaw bone resorption after the post-extraction remodeling period of 6 months, was 2- to 3-fold that of full denture wearers. When patients were edentulous for more than 10 years, the difference between the 2 latter groups disappeared. It is suggested that although the overdenture design on 2 implants offers advantages from a financial and failure rate point of view, its indications in younger patients should cautiously be evaluated in a long-term perspective concerning posterior mandibular bone resorption.

Adolescent↗

Influence of temperature and foil hardness on interocclusal tactile threshold.

Determinations of interocclusal tactile threshold levels so far have involved neither appropriate psychophysical approaches nor an assessment of the mechanical and thermal properties of the foils used. Twenty subjects (12 females) aged 18 to 50 (mean age 35) were tested for their absolute threshold level (RL). Both the method of limits and the staircase method were applied to determine the active or passive RL. For the active RL assessment, foils of different thicknesses were placed between edge-to-edge opposed incisors during gentle biting. Inner ear receptors of the blindfolded subjects were blocked by broad band noise applied through earphones, because vibrations induced by occlusal contact and conducted through bone might be perceived by these receptors. The foils presented were aluminum (Al), tin (Sn), polyester (PE) and calibrated steel (St) (thickness ranging from 8 to 50 microns) which offer different physical and thermal properties. The range of RL of the group varied between 8 microns for aluminum to 46 microns for polyester for 50% correct assessments. Increasing the foil temperature from room temperature (20 degrees C) to body temperature (35 degrees C) significantly increased the RL for conducting materials (one-way blocked ANOVA). These results indicate that temperature exchange takes place while presenting conducting foils at 20 degrees C (cold stimulus) interocclusally, which influences the RL by activating thermosensitive receptors. The passive RL determination with classical von Frey-hairs resulted in a mean axial RL of 3.0 g. Both psychophysical RL assessments (method of limits, staircase method) gave reproducible and similar results as ascertained by ANOVA. Furthermore, a positive correlation was established between active and passive RL (Pearson correlation test).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Control of an external force in leg extensions in humans.

1. We investigated the hypothesis that mono- and bi-articular muscles perform different functions: the former are chiefly dependent on their mechanical advantage, while the latter are considered to be mainly concerned with controlling the direction of an external force. 2. Seven subjects were asked to exert a constant external force in various directions from three different positions. Feedback was given on the amplitude (300 and 600 N) and direction of the force vector. 3. During each trial the position of the subject was registered. Ground reaction force and muscle activity (EMG) from the main mono- and bi-articular upper leg muscles were recorded. Link segment modelling was used to obtain net moments about the knee and hip joints. For each muscle the mechanical advantage was calculated in each force direction. 4. The task of controlling the ground reaction force was performed with little interindividual variation as reflected by the variability of the different force and EMG variables. 5. A linear relationship between the difference in activity of rectus femoris and hamstrings and the difference in net moment around the knee and hip was found. This relationship showed very high correlation coefficients of 0.96 (300 N) and 0.97 (600 N) and was independent of position. Mean correlations between this activity difference and the angle of the force vector were also high: -0.95 (300 N) and -0.94 (600 N). 6. The mono- as well as the bi-articular muscles increased in activity when a larger mechanical advantage could be obtained from them, except for the biceps femoris (short head). 7. The results support the hypothesis that bi-articular muscles have a unique role in controlling the distribution of net moments about the joints, and as a consequence, in controlling the direction of the external force exerted on the environment.

Biomechanical Phenomena↗

[Bleeding tendency and periodontal diagnosis. Evaluation of the prognostic significance of bleeding tendency for periodontal diagnosis].

Since differences in susceptibility to periodontal breakdown do exist, it is essential to predict future breakdown on the basis of a prognostic indicator. The experimental gingivitis model was chosen to investigate the clinical differences related to the degree of susceptibility to periodontal breakdown. Both bleeding upon probing and the amount of plaque seems to depend on the history of inflammatory periodontal disease. It is concluded that the bleeding/plaque ratio may act as a prognostic indicator to predict periodontal breakdown.

Dental Plaque↗

Predictors of morbidity and mortality in neonates with herpes simplex virus infections. The National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group.

BACKGROUND: In a controlled trial comparing acyclovir with vidarabine in the treatment of neonatal herpes simplex virus (HSV) infection, we found no significant difference between the treatments in adjusted mortality and morbidity. Hence, we sought to define for the entire cohort (n = 202) the clinical characteristics that best predicted the eventual outcome in these neonates. METHODS: Data were gathered prospectively at 27 centers between 1981 and 1988 in infants less than one month of age who had virologically confirmed HSV infection. We examined the outcomes by multivariate analyses of 24 variables. Disease was classified in one of three categories based on the extent of the involvement at entry into the trial: infection confined to skin, eyes, or mouth; encephalitis; or disseminated infection. RESULTS AND CONCLUSIONS: There were no deaths among the 85 infants with localized HSV infection. The mortality rate was significantly higher in the 46 neonates with disseminated infection (57 percent) than in the 71 with encephalitis (15 percent). In addition, the risk of death was increased in neonates who were in or near coma at entry (relative risk, 5.2), had disseminated intravascular coagulopathy (relative risk, 3.8), or were premature (relative risk, 3.7). In babies with disseminated disease, HSV pneumonitis was also associated with greater mortality (relative risk, 3.6). In the survivors, morbidity was most frequent in infants with encephalitis (relative risk, 4.4), disseminated infection (relative risk, 2.1), seizures (relative risk, 3.0), or infection with HSV type 2 (relative risk, 4.9). With HSV infection limited to the skin, eyes, or mouth, the presence of three or more recurrences of vesicles was associated with an increased risk of neurologic impairment as compared with two or fewer recurrences.

Consciousness↗