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Biomedical subjects

J Lane

Publications and source records attributed to J Lane.

At least 19 recordsLinked to original sources

A screening and counseling program for prevention of osteoporosis.

Prevention of osteoporosis is an increasingly salient public health concern as our society ages. This report describes the procedures used at an osteoporosis center to which people come for screening and counseling. The patients on whom this report is based were 53 non-smoking women, 1-10 years postmenopausal at the time of their first visit to the center, who chose not to undertake estrogen therapy, and who returned for a second visit in 12-18 months. They were classified as to adequacy of calcium intake (at least 750 mg/day) and exercise (at least 3 h/week of weight-bearing exercise) at both visits; complete data on calcium intake and exercise were available on 46 of the women. Bone densities were measured at the femoral neck and lumbar spine with dual energy X-ray absorptiometry, and at the distal radius with single photon absorptiometry. At the first visit, 67% of the women reported adequate exercise and 43% reported adequate calcium intake. At the second visit, the percentages in the adequate categories had increased to 74% for exercise (p = 0.06) and 70% for calcium intake (p = 0.02). Age at the first visit was inversely correlated with femoral (r = -0.40, p = 0.003) and spinal (r = -0.36, p = 0.009) bone densities; the correlation with radial bone density did not achieve significance (r = -0.27, p = 0.55). Rather than declining, as would be expected in early postmenopausal women, bone density rose slightly, but not significantly, between visits for all three sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance

Chemotherapy for nonmetastatic osteogenic sarcoma: the Memorial Sloan-Kettering experience.

PURPOSE: Adjuvant chemotherapy improves disease-free survival (DFS) for patients with osteogenic sarcoma (OS). We reviewed our experience with OS to determine prognostic factors, the role of preoperative chemotherapy and subsequent histologic response, and the role of salvage chemotherapy after poor initial response. METHODS: From 1975 to 1984, we saw 279 patients with previously untreated OS without metastasis. All patients received intensive chemotherapy and underwent surgical resection of primary tumor. Chemotherapy included high-dose methotrexate; Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH); and bleomycin, cyclophosphamide, and dactinomycin (BCD). Selected patients also received cisplatin. RESULTS: DFS was not affected by use of preoperative chemotherapy versus immediate surgery, by use of limb-sparing surgery versus amputation, age, sex, or dose intensity of chemotherapy. DFS did correlate with serum lactate dehydrogenase (LDH), alkaline phosphatase, primary tumor site, race, and histologic response to preoperative chemotherapy. There was no difference in DFS for patients with a poor histologic response who did or did not receive cisplatin, although patients who did receive cisplatin had a longer time to relapse. The 5-year DFS was 76% for patients aged less than or equal to 21 years who had extremity primary tumor and were treated with the T10 protocol. CONCLUSIONS: Intensive chemotherapy can achieve DFS for a high proportion of patients with OS. Although it is a powerful predictor of DFS, histologic response to preoperative chemotherapy cannot be assessed at diagnosis. We have not shown an ability to salvage patients with an unfavorable response. We need to increase the proportion of patients with a favorable response, identify the patients who will have an unfavorable response, and develop novel treatments to salvage poor responders.

Adolescent

Pharmacokinetics of the digoxin-quinidine interaction via mixed-effect modelling.

It was the purpose of this study to evaluate the effect of quinidine administration on the population estimates of the volume of distribution (Vdpop) and clearance (CLpop) of digoxin. The data collected on 94 patients included 230 measured serum digoxin concentrations, height, age, sex, weight (wt), serum creatinine, history of digoxin and quinidine administration and the presence or absence of congestive heart failure (CHF). Using the NONMEM software program, estimates were obtained for CLpop and Vdpop. Variables tested for inclusion in the CLpop model were creatinine clearance (CLCR), CHF, wt, ideal bodyweight, quinidine (QUIN) [both as a discrete variable and in a dose-dependent manner], and body surface area. Variables tested for inclusion in the Vdpop model were CLCR, wt, ideal bodyweight, body surface area and quinidine. During model building a p-value of 0.05 was chosen for variable inclusion. The final model was as follows: CLpop (L/h) = (3.1 + 0.0516 x CLCR) x QUIN Vdpop (L) = (4.03 + 0.0832 x CLCR) x wt F = 0.82 where F is bioavailability. In the above, QUIN is 0.567 if quinidine is being concurrently administered and 1.0 if it is not. The coefficient of variation (CV) of CLpop was 44% while that of Vdpop was 48%. The residual intrasubject CV was 26%. These results compare favourably with previously derived methods of estimating digoxin CLpop and Vdpop but may improve on those methods due to the inclusion of quinidine in the model. These better estimates should result in improved initial dosage of digoxin.

Adult

Comparing the yield of the standard Papanicolaou and endocervical brush smears.

To compare the endocervical cell yield of the standard Papanicolaou smear and endocervical brush (Cytobrush) smear, cervical cytology smears using both techniques were obtained separately from each of 491 women between Aug 1, 1987, and Jan 31, 1990. The smear provided endocervical cells from 97% of the patients, while the Papanicolaou smear provided them from 64%. The brush was unsatisfactory (no endocervical cells) in 3% of the patients. In nine patients (2%) no endocervical cells were found on either specimen. In six patients (1%) the brush smear was unsatisfactory, while endocervical cells were found on the Papanicolaou smear. The study design precluded an adequate assessment of the sensitivity for detecting abnormal cells with the addition of the brush. The addition of an endocervical brush smear to the routine Papanicolaou smear appears to provide better sampling of the endocervical canal than does the standard Papanicolaou smear alone, using a cotton-tipped applicator.

Adolescent

A radiographical and biomechanical study of demineralized bone matrix implanted into a bone defect of rat femurs with and without bone marrow.

Repair of large bone defects represents a challenge to orthopedic surgery since autogenous graft is not available in large amounts. Demineralized bone matrix (DBM) which contains bone morphogenic protein, a potent osteoinductive glycoprotein, and collagen, an osteoconductive matrix, may be an effective substitute for these graft materials. Bone marrow which contains osteoprogenitor cells could potentiate the osteoinductive and osteoconductive properties of demineralized bone matrix. This study tested the ability of demineralized bone matrix with and without bone marrow to bridge large segmental defects, and evaluated the results both radiographically and biomechanically as compared to autogenous (isogeneic) cancellous bone graft. Demineralized bone-matrix segments implanted into a plated femoral segmental defect in rats resulted in firm union in most animals. Bone marrow significantly enhanced bone formation of demineralized bone-matrix implants at an early stage but with time, differences between bone marrow-augmented and bone marrow-deprived demineralized bone implants were no longer demonstrable radiographically and biomechanically. Newly formed bone had about 50% of the strength of the contralateral control bones. Femurs implanted with cancellous bone isografts had similar evidence of absolute union rate, radiographic and mechanical properties as DBM-implanted femurs.

Animals

Gallium nitrate for advanced Paget disease of bone: effectiveness and dose-response analysis.

OBJECTIVE: To evaluate whether a brief course of treatment with gallium nitrate can reduce biochemical parameters of accelerated bone turnover in patients with advanced Paget disease. DESIGN: Unblinded trial, decreasing dose schedules of gallium nitrate. SETTING: University hospital with primary orthopedic and metabolic bone disease specialty. PATIENTS: Ten patients with advanced Paget disease who had previously received conventional therapy consisting of calcitonin, etidronate, or mithramycin. INTERVENTIONS: Five patients were entered into each of three dose schedules: 2.5 mg/kg body weight per day by continuous intravenous infusion for 7 days; 0.5 mg/kg per day for 14 days by subcutaneous injection; and 0.25 mg/kg per day for 14 days by subcutaneous injection. Several patients were treated with different dose schedules. Patients were followed until relapse. RESULTS: Fifteen courses of treatment were administered to ten patients. Reductions in serum alkaline phosphatase and urinary hydroxyproline excretion were observed after treatment with each dose schedule. After treatment with high, intermediate, and low doses, the median maximum decreases in serum alkaline phosphatase activity were 49%, 39%, and 18%, respectively. The median maximum decreases in urinary hydroxyproline excretion were 50%, 52%, and 16%, respectively. The maximum decrease in urinary hydroxyproline excretion occurred within a median of 2 weeks from the start of treatment, whereas the maximum decrease in serum alkaline phosphatase activity occurred substantially later at a median of 6 weeks. All treatment schedules were well tolerated. Response duration was highly variable (range, 6 to 42 weeks). CONCLUSIONS: Short-term treatment with gallium nitrate can reduce biochemical parameters of disease activity in patients with advanced Paget disease of bone. Larger trials using low-dose intermittent treatment schedules are required to evaluate the safety and effectiveness of this therapy.

Aged

A mouse model of the aniridia-Wilms tumor deletion syndrome.

Deletion of chromosome 11p13 in humans produces the WAGR syndrome, consisting of aniridia (an absence or malformation of the iris), Wilms tumor (nephroblastoma), genitourinary malformations, and mental retardation. An interspecies backcross between Mus musculus/domesticus and Mus spretus was made in order to map the homologous chromosomal region in the mouse genome and to define an animal model of this syndrome. Nine evolutionarily conserved DNA clones from proximal human 11p were localized on mouse chromosome 2 near Small-eyes (Sey), a semidominant mutation that is phenotypically similar to aniridia. Analysis of Dickie's Small-eye (SeyDey), a poorly viable allele that has pleiotropic effects, revealed the deletion of three clones, f3, f8, and k13, which encompass the aniridia (AN2) and Wilms tumor susceptibility genes in man. Unlike their human counterparts, SeyDey/+ mice do not develop nephroblastomas. These findings suggest that the Small-eye defect is genetically equivalent to human aniridia, but that loss of the murine homolog of the Wilms tumor gene is not sufficient for tumor initiation. A comparison among Sey alleles suggests that the AN2 gene product is required for induction of the lens and nasal placodes.

Animals

Clindamycin effect on glycocalyx production in experimental viridans streptococcal endocarditis.

Abundant glycocalyx production by viridans streptococci in the rabbit model of endocarditis has been associated with delayed antimicrobial sterilization. Enzymatic digestion of the glycocalyx with dextranase enhances antibiotic activity. The effect of clindamycin (30 mg/kg, subcutaneous, three times daily) was studied in rabbits with experimental aortic valve endocarditis caused by high glycocalyx-producing viridans streptococci. Animals receiving clindamycin had smaller vegetations that were sterilized more quickly than did controls or animals receiving penicillin or dextranase alone (P less than .001). Penicillin plus dextranase treatment allowed greater bacterial killing than penicillin alone and did not differ significantly from clindamycin treatment. Electron micrographs revealed markedly less cell-adherent glycocalyx on organisms grown in vitro treated with clindamycin versus penicillin and controls. It is hypothesized that clindamycin inhibits glycocalyx production in vivo, allowing better antimicrobial penetration in the infected cardiac vegetation.

Animals

Liver tryptophan pyrrolase. A major determinant of the lower brain 5-hydroxytryptamine concentration in alcohol-preferring C57BL mice.

The lower brain 5-hydroxytryptamine concentration in alcohol-preferring C57BL, compared with -non-preferring CBA, mice is caused by a decrease in circulating tryptophan availability to the brain secondarily to a higher liver tryptophan pyrrolase activity associated with a higher circulating corticosterone concentration. Activity or expression of liver tryptophan pyrrolase and/or their induction by glucocorticoids may be important biological determinants of predisposition to alcohol consumption.

Alcoholism

The MRL +/+ mouse: a new model of tubular aggregates which are gender- and age-related.

Congenic mice of the MRL +/+ substrain provide an animal model for study of tubular aggregates in skeletal muscle. Tubular aggregates appear limited only to males of the MRL +/+ strain and are not found in other strains, including MRL +/-, MRL lpr/lpr, BXSB/MpJ, BALB/c, SJL/J, AJ, or C3H HEJ. This strain-specific occurrence, and the gradually increasing abundance of tubular aggregates after 6 months of age until virtually all type II myofibers are affected by 2 years, implies that both genetic and developmental factors are necessary for the occurrence of tubular aggregates. These two factors are not sufficient, however, since hormonal alteration by male castration nearly completely prevents the expression of tubular aggregates. Parallels are drawn with how expression of tubular aggregates is limited largely to males in diverse acquired and hereditary human neuromuscular disorders.

Animals

Anti-SS-A/Ro SS-B/La antibodies bind to neonatal rabbit cardiac cells and preferentially inhibit in vitro cardiac repolarization.

The neonatal lupus syndrome is the most common cause of isolated congenital heart block. There is, at present, little information about the putative role of anti-SS-A/Ro SS-B/La antibodies in the pathogenesis of congenital heart block in the neonatal lupus syndrome. Using an in vitro experimental model, the present study was designed to test the hypothesis that IgG antibodies in the sera of anti-SS-A/Ro SS-B/La-positive mothers of infants with isolated congenital heart block bind to and affect the transmembrane action potential of rabbit cardiac tissue. The results demonstrate a preferential inhibition of membrane repolarization (ADP-50 and ADP-90) and staining of cardiac cells within the neonatal, in contrast to the adult, rabbit heart by sera and IgG-enriched fractions from anti-SS-A/Ro SS-B/La-positive individuals. The results of the electrophysiologic studies demonstrate a pathophysiologic role for the IgG fraction of anti-SS-A/Ro SS-B/La-positive maternal sera in inhibiting neonatal rabbit cardiac repolarization. It is possible that antibodies to similar determinants expressed on the cell membrane of cardiac-conducting cells also may play a pathophysiologic role in the development of idiopathic congenital heart block in humans.

Animals