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Biomedical subjects

P Lang

Publications and source records attributed to P Lang.

At least 127 records · Page 7Linked to original sources

Neurotropic cutaneous tumors of the head and neck.

OBJECTIVE: To determine the outcomes of patients with neurotropic cutaneous tumors of the head and neck. DESIGN: A retrospective review was conducted of 7852 charts of patients who underwent micrographically controlled excisions of skin cancers of the head and neck between 1984 and 1995, identifying neurotropic tumors and the outcomes of their treatments. SETTING: Tertiary care center (university hospital). PATIENTS: Thirty-seven patients with neurotropic tumors were identified (and confirmed by secondary histological review), constituting 0.47% of all patients. The median age at presentation was 68 years and all except an albino were white. Nine patients had basal cell carcinomas and 28 had squamous cell carcinomas. Twenty-five patients (69%) were referred after at least 1 prior excision was performed a median of 16 months previously. INTERVENTION: All patients underwent micrographic mapping and excision of the cutaneous portion of the tumor. As necessitated by tumor spread, additional soft tissue, skull base, and/or intracranial surgery and postoperative irradiation were also conducted. MAIN OUTCOME MEASURES: Thirty-four patients (3 patients were unavailable for follow-up) were assessed by physician examination a minimum of 19 months after treatment (median, 33 months). RESULTS: Of 25 patients with extracranial disease only, 19 had no evidence of disease during follow-up and 1 died of intercurrent disease at 20 months without evidence of tumor persistence. Of the 9 patients with intracranial neurotropic tumors at the time of presentation, 1 remained with no evidence of disease, 1 died of intercurrent disease at 21 months without evidence of tumor persistence, and the other 7 either died of or are living with an intracranial tumor. CONCLUSIONS: Micrographic tissue mapping to detect and then encompass neurotropic cutaneous malignancies, along with conventional surgery for deeper tumor invasions and irradiation in selected cases, was successful in 19 patients (76%) with an extracranial tumor. For those with neurotropic tumors approaching or penetrating the skull base, the prognosis was poor regardless of therapy method.

Aged↗

High resolution magnetic resonance imaging of the calcaneus: age-related changes in trabecular structure and comparison with dual X-ray absorptiometry measurements.

A high-resolution magnetic resonance imaging (MRI) protocol, together with specialized image processing techniques, was applied to the quantitative measurement of age-related changes in calcaneal trabecular structure. The reproducibility of the technique was assessed and the annual rates of change for several trabecular structure parameters were measured. The MR-derived trabecular parameters were compared with calcaneal bone mineral density (BMD), measured by dual X-ray absorptiometry (DXA) in the same subjects. Sagittal MR images were acquired at 1.5 T in 23 healthy women (mean age: 49.3 +/- 16.6 [SD]), using a three-dimensional gradient echo sequence. Image analysis procedures included internal gray-scale calibration, bone and marrow segmentation, and run-length methods. Three trabecular structure parameters, apparent bone volume (ABV/TV), intercept thickness (I.Th), and intercept separation (I.Sp) were calculated from the MR images. The short- and long-term precision errors (mean %CV) of these measured parameters were in the ranges 1-2% and 3-6%, respectively. Linear regression of the trabecular structure parameters vs. age showed significant correlation: ABV/TV (r2 = 33.7%, P < 0.0037), I.Th (r2 = 26.6%, P < 0.0118), I.Sp (r2 = 28.9%, P < 0.0081). These trends with age were also expressed as annual rates of change: ABV/TV (-0.52%/year), I.Th (-0.33%/year), and I.Sp (0.59%/year). Linear regression analysis also showed significant correlation between the MR-derived trabecular structure parameters and calcaneal BMD values. Although a larger group of subjects is needed to better define the age-related changes in trabecular structure parameters and their relation to BMD, these preliminary results demonstrate that high-resolution MRI may potentially be useful for the quantitative assessment of trabecular structure.

Absorptiometry, Photon↗

Indirect MR arthrography: techniques and applications.

Indirect MR arthrography is a simple noninvasive alternative to direct MR arthrography and can potentially alter the diagnostic work-up of several diseases. Based on current knowledge, these diseases include rotator cuff tears. glenoid labrum tears, recurrent tears of the menisci and classification of osteochondritis dissecans. The technique is recommended for inclusion in the MRI diagnostic array, and may obviate the need for invasive direct MR arthrography. The technique and applications of indirect MR arthrography are summarized in this article, based on our own experiences and that described in the current literature.

Adipose Tissue↗

An HSV-1 vector containing the rat tyrosine hydroxylase promoter enhances both long-term and cell type-specific expression in the midbrain.

A defective herpes simplex virus type one (HSV-1) vector that contains a 6.8-kb fragment of the rat tyrosine hydroxylase promoter (pTHlac-7kb) was examined for its capability to target catecholaminergic cell type-specific expression in the CNS. Cell type-specific expression was assessed by comparison with a control vector (pHSVlac) that uses the HSV-1 immediate early 4/5 promoter to support expression in multiple cell types. In initial experiments comparing expression in catecholaminergic and noncatecholaminergic cell lines, pTHlac-7kb supported a seven- to 20-fold increase in reporter gene expression in catecholaminergic cell lines. Four days after stereotactic injection into the midbrain of adult rats, pTHlac-7kb supported a 10-fold targeting of beta-galactosidase expression to tyrosine hydroxylase-expressing neurons in the substantia nigra pars compacta compared with pHSVlac. Expression from pTHlac-7kb was stably maintained for 6 weeks with no significant changes in the pattern of expression. Long-term expression from pTHlac-7kb was confirmed by RNA and DNA analysis. In contrast, reporter gene expression in the midbrain from pHSVlac decreased approximately 30-fold between 4 days and 6 weeks after gene transfer. Thus, within the context of this HSV-1 vector system, the tyrosine hydroxylase promoter enhanced cell type-specific expression and contributed to stable, long-term expression of a recombinant gene product in neurons. The capability to target recombinant gene expression to catecholaminergic neurons in specific brain areas may be useful for studies on the roles of these neurons in brain physiology and behavior.

Animals↗

Positive selection and transplantation of peripheral CD34+ progenitor cells: feasibility and purging efficacy in pediatric patients with neuroblastoma.

Peripheral stem cells were mobilized and collected in 20 children with stage 4 neuroblastoma. A total of 37 leukaphereses were performed in the 20 patients. The mean number of collected cells was 5.6 +/- 2.4 x 10(8)/kg (range 1.9-10.5), and the number of collected CD34+ progenitors was 6.1 +/- 6.3 x 10(6)/kg (range 0.75-21.7). CD34-positive selection was performed using the CellPro method. Of the adsorbed cells, 42 +/- 20% (range 4.3-76.6) stained positively for CD34, and the number of positively selected CD34+ cells was 2.0 +/- 1.9 x 10(6)/kg (range 0.09-7.1). The mean recovery of CD34+ cells was 36 +/- 20% (range 6-67). For detection of contaminating neuroblastoma cells before and after CD34-positive selection, a murine antidisialoganglioside GD2 antibody (14.G2a) was used, followed by the alkaline phosphatase antialkaline phosphatase (APAAP) method. Before the positive selection, various numbers of contaminating neuroblastoma cells were found in the leukaphereses of 7 patients. After positive selection, neuroblastoma cells were still detectable in all 7 patients, with a mean log depletion of tumor cells of 1.41 +/- 0.45 (range 0.69-2.13). In 1 patient, contaminating neuroblastoma cells were found only after CD34-positive selection. In 15 of the 20 patients, high-dose chemotherapy was performed, and positively selected CD34+ cells were reinfused in 12 patients. In 10 of these, the mean time to reach > 0.5 x 10(9)/L granulocytes was 12.3 +/- 1.7 days (range 10-16). One patient died at day 7 due to sepsis, and in 1 patient the backup was given at day 15. Because of the low number of collected CD34+ cells, 3 patients were grafted with a combination of unmanipulated PBSC and CD34+ progenitors. In summary, we have shown that positive selection of peripheral CD34+ progenitors is feasible in pediatric patients. However, strategies to improve the recovery of the CD34+ cells and the purging efficacy of this method (i.e., higher enrichment of CD34+ cells, combination of positive and negative selection methods) should be evaluated further.

Animals↗

Comparisons of noninvasive bone mineral measurements in assessing age-related loss, fracture discrimination, and diagnostic classification.

The purpose of this study was to examine the commonly available methods of noninvasively assessing bone mineral status across three defined female populations to examine their interrelationships, compare their respective abilities to reflect age- and menopause-related bone loss, discriminate osteoporotic fractures, and classify patients diagnostically. A total of 47 healthy premenopausal (age 33 +/- 7 years), 41 healthy postmenopausal (age 64 +/- 9 years), and 36 osteoporotic postmenopausal (age 70 +/- 6 years) women were examined with the following techniques: (1) quantitative computed tomography of the L1-L4 lumbar spine for trabecular (QCT TRAB BMD) and integral (QCT INTG BMD) bone mineral density (BMD); (2) dual X-ray absorptiometry of the L1-L4 posterior-anterior (DXA PA BMD) and L2-L4 lateral (DXA LAT BMD) lumbar spine, of the femoral neck (DXA NECK BMD) and trochanter (DXA TROC BMD), and of the ultradistal radius (DXA UD BMD) for integral BMD; (3) peripheral QCT of the distal radius for trabecular BMD (pQCT TRAB BMD) and cortical bone mineral content (BMC) (pQCT CORT BMC); (4) two radiographic absorptiometric techniques of the metacarpal (RA METC BMD) and phalanges (RA PHAL BMD) for integral BMD; and (5) two quantitative ultrasound devices (QUS) of the calcaneus for speed of sound (SOS CALC) and broadband ultrasound attenuation (BUA CALC). In general, correlations ranged from (r = 0.10-0.93) among different sites and techniques. We found that pQCT TRAB BMD correlated poorly (r < or = 0.46) with all other measurements except DXA UD BMD (r = 0.62,p < or = 0.0001) and RA PHAL BMD (r = 0.52, p < or = 0.0001). The strongest correlation across techniques was between QCT INT BMD and DXA LAT BMD (r = 0.87, p < or = 0.0001), and the weakest correlation within a technique was between pQCT TRAB BMD and pQCT CORT BMC (r = 0.25,p < or = 0.05). Techniques showing the highest correlations with age in the healthy groups also showed the greatest differences among groups. They also showed the best discrimination (as measured by the odds ratios) for the distinction between healthy postmenopausal and osteoporotic postmenopausal groups based on age-adjusted logistic regression analysis. For each anatomic site, the techniques providing the best results were: (1) spine, QCT TRAB BMD (annual loss, -1.2% [healthy premenopausal and healthy postmenopausal]); Student's t-value [not the T score], 5.4 [healthy postmenopausal vs. osteoporotic postmenopausal]; odds ratio, 43 [age-adjusted logistic regression for healthy postmenopausal vs. osteoporotic postmenopausal]); (2) hip, DXA TROC BMD (-0.46; 3.5; 2.2); (3) radius, DXA UD BMD (-0.44; 3.3; 1.9) and pQCT, CORT BMC (-0.72; 2.9; 1.7); (4) hand, RA PHAL (-0.51; 3.6; 2.0); and (5) calcaneus, SOS (-0.09; 3.4; 2.1) and BUA (-0.52; 2.6; 1.7). Despite these performance trends, the differences among sites and techniques were statistically insignificant (p > 0.05) using age-adjusted receiver operating characteristic (ROC) curve analysis. Nevertheless, kappa score analysis (using -2.0 T score as the cut-off value for osteopenia and -2.5 T score for osteoporosis) showed that in general the diagnostic agreement among these measurements in classifying women as osteopenic or osteoporotic was poor, with kappa scores averaging about 0.4 (exceptions were QCT TRAB/INTG BMD, DXA LAT BMD, and RA PHAL BMD, with kappa scores ranging from 0.63 to 0.89). Often different patients were estimated at risk by using different measurement sites or techniques.

Absorptiometry, Photon↗

The treatment of chronic pain by epidural spinal cord stimulation--a 15 year follow up; present status.

Pain is necessary for survival but chronic pain is disabling and causes significant health and economic problems. This study provides an understanding of the future for spinal cord stimulation. Stimulation by means of chronically implanted electrodes, was carried out in 200 patients with pain of varied benign organic etiology. In 177 of them, pain was confined to the failed back syndrome. Most patients were referred by a Pain Management Service. 226 epidural implants were used: 80 unipolar, 59 Resume, 12 bipolar, and 75 quadripolar. Patients were followed for periods of 6 months to 12 years, with a mean follow-up of 44 months. 84 patients (42%) were able to control their pain by stimulation alone, 22 patients (11%) needed occasional analgesic supplements along with their stimulation program. Pain secondary to failed back syndrome, multiple sclerosis, peripheral vascular disease, sympathetic dystrophy and diabetic neuropathy responded favorably. Pain due to cauda equina injury, paraplegic pain and phantom limb pain responded poorly. Complications included wound infection, displaced or fracture electrode, and fibrosis at the stimulating tip. Spinal cord stimulation has proven to be effective in the treatment of chronic benign pain.

Adult↗

[Passive smoking in children up to 5 years of age].

Passive smoking is a major health risk in young children. We investigated the percentage of children with mothers and/or fathers who reported regular smoking. Data are the national and regional health surveys of the German Cardiovascular Prevention Study (GCP) conducted from 1984 to 1992 in West Germany. 2538 mothers aged 25-40 years were included. The prevalence of passive smoking in children due to smoking mothers was 33.6% 55.4% of the children up to 5 years lived in households with at least one smoking parent member. In 23.4% of these households both parents were smokers. If only one member of the parents smoked this was in two out of three cases the father. 28.2% of mothers with a child younger than one year were current smokers. This prevalence rate increased with the age of the youngest child up to 35.6% for mothers, whose youngest child was 5 years old. Multiple logistic regression analysis was performed to investigate the association between smoking behaviour and the following variables: mother's age, social class, family status, community size and year of the survey. It was found that lower social class members, unmarried or divorced mothers and inhabitants of large cities reported significantly more often regular current smoking. These results underscore the importance of special intervention programs to reduce smoking in parents with young children.

Child, Preschool↗

Selective tumor irradiation by infusional brachytherapy in nonresectable pancreatic cancer: a phase I study.

PURPOSE: Selective high-dose radiation of solid tumors has been a goal of radiation oncology. The physiological barriers of solid tumors (high interstitial tumor pressure, reduced tumor vascularity, and poor perfusion) have been major barriers in achieving significant tumor dose of systemically infused radioconjugates. Direct tumor infusional brachytherapy overcomes these barriers and leads to selective high tumor doses. METHODS AND MATERIALS: The development of interstitial tumor infusion of macroaggregated albumin (MAA) followed by colloidal chromic phosphate 32P has overcome solid tumor obstacles in 47 patients with nonresectable pancreatic cancer in a Phase I dose escalation study. The colloidal 32P infusion was followed by external radiation and five fluorouracil. RESULTS: Of the 28 patients with cancer limited to the pancreas, 15 of 16 patients retained 86-100% (mean 96%) of the infused colloidal 32P isotope. While the other 12 patients had partial shunting to the liver, shunting to the liver was due to high interstitial resistance with tumor dose deposition of 17-88% (mean 52 %). Of the 19 patients with metastatic pancreas cancer, colloidal 32P tumor deposition ranged from 22 to 100% of the infused dose (mean 79%). The less than optimal tumor deposition led to our increasing the MAA from 600,000 to 1.5-2.5 million particles. Interstitial dexamethasone 2 mg and later 4 mg was infused first and prevented liver shunting by somehow reducing tumor resistance. The median survival in 28 Phase I patients with nonresectable pancreas cancer without metastasis, was 12 months. No significant toxicity occurred when treatment was limited to two infusions with as much as 30 mCi each. The maximum tumor dose was 17,000 Gy (1.700,000 cGy). In 19 nonresectable pancreatic cancer patients with metastasis, a 6.9 months median survival was observed. CONCLUSIONS: Infusional brachytherapy is an outpatient procedure that delivers high-dose radiation selectively to pancreatic cancer. Results of the Phase I study in nonresectable pancreas cancer has led to a national multiinstitutional Phase II trial.

Adult↗

Nonprocurement of transplantable organs in a tertiary care hospital: a focus on sociological causes.

BACKGROUND: The purpose of this study was to investigate prospectively the medical and organizational causes of nonprocurement of transplantable organs and to provide explicit information on the determining factors of family response to donation request. METHODS: Medical causes investigated were age, human immunodeficiency virus, human T-cell lymphoma virus and hepatitis C virus status, documented malignancy, and chronic cardiac or renal failure. Organizational aspects investigated were cause and place of death and number of referrals. Sociological aspects were investigated by semidirective interviews with the families of the deceased. RESULTS: A total of 105 brain-dead patients and 42 families were included. Of the 105 patients, 9 were not eligible for donation because of medical reasons; cardiac arrest occurred before organ procurement in 6 cases. Denial of consent from the coroner occurred in 7 cases. Consent was requested from the families in 82 cases, obtained in 53 cases, and denied in 29 cases. Consent to donation was associated with openness of the process, information about brain death and transplantation, previously stated will of the deceased, favorable attitude of the deceased toward the medical profession, and a generally altruistic attitude of the deceased. Denial of donation was associated with poor understanding of brain death and fear of being deprived of the deceased body. CONCLUSIONS: Practical implications of this study include encouraging people to state their attitudes toward organ donation and improving the level of information available to the general public on the meaning of brain death and on the medical aspects of organ transplantation.

Hospitals, Special↗

[Economic contribution of mofetil mycofenolate as preventive immunosuppressive treatment after renal transplantation from cadaver].

OBJECTIVES: The economic impact resulting from the clinical consequences of immunosuppressive strategy using mycophenolate mofetil in new renal transplant recipients was conducted considering the viewpoint of the health insurance system. METHODS: The analysis was based on the results of three controlled randomized double-blind clinical trials comparing mycophenolate mofetil with placebo or azathioprine in 1003 out of 1493 included patients respectively. Health care costs associated with each event were determined by 7 French experts in renal transplantation working in six different hospitals. Direct cumulative costs for each strategy were compared. RESULTS: The studies demonstrated a difference in the incidence of acute rejection and treatment failures whatever the cause. The three trials showed that, compared with current strategies, use of mycophynolate mofetil in the immunosuppression protocol generated a 19 to 38% cost reduction during the 6 months after transplantation. Cost reduction resulted from lower incidence of acute rejection and the subsequent nephrectomics and dialysis sessions. The sensitivity analysis on the most important cost factors-cost of hospitalization per day and number of hospitalization days-confirmed strength of the results. CONCLUSION: Use of mycophenolate mofetil in the immunosuppressive prophylaxis protocol after renal transplantation allows a reduction in the direct costs during the 6 months following transplantation.

Adult↗

Expression of the calcium-binding protein, parvalbumin, in cultured cortical neurons using a HSV-1 vector system enhances NMDA neurotoxicity.

Calcium-binding proteins (CaBPs) are a family of proteins having a unique distribution in the brain and are thought to be important in buffering intracellular calcium. Glutamate neurotoxicity is a process by which the over-activation of glutamate receptors can cause the influx of excessive extracellular calcium and neuronal cell death. It has been proposed that neurons containing CaBP may be more resistant to glutamate neurotoxicity due to their increased ability to buffer calcium. Using a herpes simplex virus-1 (HSV-1) vector system we packaged the CaBP gene, parvalbumin, or the marker gene, beta-galactosidase (beta-gal), correctly in viron particles, which were found upon infection to express mRNA specific to these vectors. PC12 and neocortical cultures showed strong immunohistochemical staining for either beta-gal or parv. The cortical cultures stained positively for endogenous glutamate decarboxylase, a marker for GABAergic neurons, but not for endogenous parvalbumin, indicating that parvalbumin was being expressed ectopically from the HSV-1 vector. Interestingly, the expression of parvalbumin increased cortical culture's susceptibility to N-methyl-D-aspartate-induced neurotoxicity. This increase in neurotoxicity was not due to the wild-type virus or the helper virus which accompanies the packaging of these vectors. We speculate that the ectopic expression of parvalbumin in cortical cultures may be increasing glutamate release which in turn increases cell death.

Animals↗