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Biomedical subjects

L Klein

Publications and source records attributed to L Klein.

At least 55 records · Page 3Linked to original sources

Long term follow-up and late complications of 2-chlorodeoxyadenosine in previously treated, advanced, indolent non-Hodgkin's lymphoma.

BACKGROUND: The aim of this study was to determine the long term outcome and toxicities after the administration of 2-chlorodeoxyadenosine (2-CdA) to patients with previously treated, advanced, indolent non-Hodgkin's lymphoma (NHL). METHODS: Twenty-two patients (median age, 55 years) with relapsed or refractory low grade NHL (median disease duration, 2.8 years) were treated with 2-CdA by continuous infusion at 0.1 mg/kg/day over 5 or 7 days every 28 days, for a maximum of 6 cycles. RESULTS: The overall response rate was 45%. Two patients (9%) achieved a complete response (CR), 8 patients (36%) achieved a partial response, and 12 patients (55%) had no response. The two patients achieving CR have remained in CR for 46 and 38 months, respectively. Freedom from treatment failure at 24 months was 32%. Overall survival at 24 months was 59%. Three patients developed second malignancies: acute myelogenous leukemia (AML), myelodysplastic syndrome, and a cutaneous lymphoproliferative disorder. Fourteen patients have died after a median follow-up of 28 months (range, 3.9-49.2 months) due to progressive NHL (11 patients), infection (2 patients), and AML (1 patient). CONCLUSIONS: 2-CdA is an active agent for patients with previously treated, advanced, indolent NHL and may result in lasting remissions. Late complications following treatment may include delayed bacterial, fungal, or viral infection. Determination of whether the second malignancies that occurred in three patients reported herein were related to treatment with 2-CdA will require further study.

Adolescent↗

Domestic violence screening practices of obstetrician-gynecologists.

OBJECTIVE: To ascertain the current knowledge base and screening practices of obstetrician-gynecologists in the area of domestic violence. METHODS: We mailed a survey to 189 ACOG Fellows who are members of the Collaborative Ambulatory Research Network. Questionnaires were also mailed to a random sample of 1250 nonmember Fellows. RESULTS: Obstetrician-gynecologists are aware of the nature of domestic violence and are familiar with common symptomatology that may be associated with domestic violence. For pregnant patients, 39% of respondents routinely screen at the first prenatal visit; 27% of respondents routinely screen nonpregnant patients at the initial visit. Screening is most likely to occur when the obstetrician-gynecologist suspects a patient is being abused, both during pregnancy (68%) and when the patient is not pregnant (72%). Only 30% of obstetrician-gynecologists received training on domestic violence during medical school; 37% received such instruction during residency training. The majority (67%) have received continuing education on the subject. Years since training and personal experiences with intimate-partner violence were associated with increased screening practices. CONCLUSION: Routine screening of all women for domestic violence has been recommended by ACOG for more than a decade. The majority of obstetrician-gynecologists screen both pregnant and nonpregnant patients when they suspect abuse. However, with universal screening, more female victims of violence can be identified and can receive needed services.

Adult↗

Model-guided labeling of coronary structure.

Assigning anatomic labels to coronary arteries in X-ray angiograms is an important task in medical imaging, motivated by the desire to standardize the assessment of coronary artery disease and to facilitate the three-dimensional (3-D) reconstruction and visualization of the coronary vasculature. However, automatic labeling poses a number of significant challenges, including the presence of noise, artifacts, competing structures, misleading visual cues, and other difficulties associated with a dynamic and inherently complex structure. We have developed a model-guided approach that addresses these challenges and automatically labels the vascular structure in coronary angiographic images. The approach consists of two models: 1) a symbolic model, represented through a directed acyclic graph, that captures vascular tree hierarchies and branch interrelationships and 2) a generalized 3-D model that captures spatial and geometric relationships. Importantly, the approach detects ambiguities (such as vessel overlaps) that may be found in a frame of a ciné sequence, and resolves these ambiguities by considering the information derived from other (unambiguous) frames in the temporal sequence, employing dynamic programming methods to match the image features found in the different (ambiguous and unambiguous) frames. This paper presents this model-guided labeling algorithm and discusses the experimental results obtained from implementing and applying the resulting labeling system to a variety of clinical images. The results indicate the feasibility of achieving robust and consistently accurate image labeling through this model-guided, temporal disambiguation method.

Coronary Angiography↗

Selection of a broad repertoire of CD4+ T cells in H-2Ma0/0 mice.

According to past reports, H-2Ma0/0 mice express a single major histocompatiblity complex class II molecule, A(b), heavily loaded with a single peptide derived from the invariant chain, CLIP. Despite the highly restricted diversity of the class II:peptide complexes expressed on thymic stromal cells in the mutant animals, a large and diverse population of CD4+ T cells is positively selected. However, two important issues remained unresolved and are addressed here: Just how preponderant is CLIP occupancy of the class II molecules from H-2M0/0 mice? How extensive and functionally competent is the CD4+ population selected in the mutant animals? Our results argue that a single class II:peptide complex can select a very broad, though not complete, repertoire of CD4+ T cells.

Animals↗

Hyperbaric dye solution distribution characteristics after pencil-point needle injection in a spinal cord model.

BACKGROUND: The flow-rate limiting and directional characteristics of caudally directed microcatheters, which lead to intrathecal maldistribution of hyperbaric 5% lidocaine, are believed to have contributed to at least 11 cases of cauda equina syndrome. The authors investigated the distribution characteristics of hyperbaric dye solutions via caudally directed side port needles at various rates of injection in a spinal cord model to determine the potential for maldistribution. METHODS: Using a digital video image processing technique, we injected a hyperbaric solution of phthalocyanine blue dye through caudally directed side-port needles into a supinely oriented transparent spinal canal model filled with simulated cerebrospinal fluid. Injections via commonly used spinal needles (24-gauge and 25-gauge Sprotte, and 25-gauge and 27-gauge Whitacre) were recorded using five injection rates (2, 4, 6, 8, and 16 ml/min). RESULTS: For all needles tested, injection rate had a significant effect on the peak dye concentration (P < 0.0001). Injection rates > or = 6 ml/min (2 ml/20 s) resulted in peak dye concentrations of less than 168 mg/1 (extrapolated concentration of 1% lidocaine). Injection via the 24-gauge Sprotte needle, which has a larger orifice area and internal diameter, resulted in significantly lower peak dye concentrations than via the smaller Whitacre needles tested (P < 0.05). CONCLUSIONS: Sacral maldistribution could be minimized by using injection rates > or = 6 ml/min (2 ml/20 s), for all of the side-port spinal needles used in this model study. When very slow injection rates (2 ml/min) are used, peak dye concentrations varied inversely and significantly with needle internal diameter and orifice area.

Anesthetics, Local↗

Correlation between self-reported cocaine use and urine toxicology in an inner-city prenatal population.

To determine the prevalence of recent cocaine use and the accuracy of self-reported use, the results of a urine assay for the major cocaine metabolite benzoylecgonine were compared with self-reported cocaine use in an inner-city prenatal population offered routine voluntary urine toxicology screening at the time of registration for prenatal care. During a 1-year period, 6866 women registered for prenatal care and 5200 (76%) consented to urine assays for cocaine metabolites. Of the women consenting to urine assays, 253 (5%) had positive assays for benzoylecgonine. Women with positive assays were significantly more likely than those with negative assays to be older (mean [SD] 27 [5] versus 23 [6] years), black, single, and unemployed. In addition, women with positive assays were significantly more likely to be multiparous, report > two sexual partners in the previous year, and acknowledge a history of a sexually transmitted disease (STD). Forty-seven percent of women with positive assays acknowledged cocaine use in the 6 months prior to sampling. Women with positive assays who denied cocaine use were significantly more likely than those who admitted use to be younger (mean [SD] 26 [5] versus 28 [4] years), to report > or = two sexual partners in the past year, and acknowledge a history of an STD. This analysis revealed a poor correlation between self-reported cocaine use and the results of urine assays for cocaine metabolites among women seeking prenatal care in an inner-city institution.

Cocaine↗

Critical biological determinants of incorporation of non-vascularized cortical bone grafts. Quantification of a complex process and structure.

Our goal in this study was to evaluate the effects of and the interaction between the hypothesized principal determinants of the incorporation of grafts: antigenicity and treatment of the graft. We implanted fresh and frozen cortical bone grafts that were matched for both major and non-major histocompatibility complex antigens (syngeneic grafts), matched for major but not for non-major histocompatibility complex antigens (minor mismatch), and mismatched for both major and non-major histocompatibility complex antigens (major mismatch). We used a rat model with an eight-millimeter segmental defect in the femur. The construct was stabilized with a plastic plate, threaded Kirschner wires, and cerclage wires. We evaluated the grafts at one, two, and four months after implantation. We measured the immune response; assessed the incorporation of the graft with use of histological examination, biomechanical testing, and quantitative isotopic kinetics; and statistically analyzed the effects of and the interactions among three independent variables: time, the degree of matching for major histocompatibility complex antigens, and the treatment of the graft (whether it was fresh or frozen). These three independent variables had profound effects on the pattern, rate, and quality of the incorporation of the graft. Two-way and three-way interactions among these variables were also noted. Serial changes in every dependent variable were observed with time. Systemic antibody specific for donor antigens was measurable only in the serum of animals that had a major mismatch, but freezing markedly attenuated the systemic antibody response. Revascularization was profoundly affected by histocompatibility-antigen matching; the syngeneic grafts were revascularized more quickly and to a greater degree than the grafts with either a minor or a major mismatch. Freezing significantly (p < 0.001) reduced the revascularization of the syngeneic grafts but had no discernible effect on the grafts with a minor mismatch.

Animals↗

Pseudodyssynergia (contraction of the external sphincter during voiding) misdiagnosed as chronic nonbacterial prostatitis and the role of biofeedback as a therapeutic option.

PURPOSE: Chronic lower urinary tract symptoms in young men are often attributed to misdiagnosed chronic nonbacterial prostatitis. We analyzed contraction of the external urinary sphincter during voiding (pseudodyssynergia) as an etiology of voiding dysfunction in men with misdiagnosed chronic prostatitis. MATERIALS AND METHODS: The video urodynamic studies of 43 men 23 to 50 years old with chronic voiding dysfunction secondary to pseudodyssynergia performed between January 1990 and June 1996 were retrospectively analyzed. Pseudodyssynergia was diagnosed based on several criteria, including electrical activity of the external sphincter during voiding in the absence of abdominal straining, and brief and intermittent closing of the membranous urethra during voiding detected by electromyography and fluoroscopy. Patients with bacterial infection or excessive leukocytes in expressed prostatic secretions were excluded from the study. RESULTS: Of the patients 39 (91%) were firstborn men. Duration of symptoms ranged from 17 to 146 months (mean 43.6). Average number of previous antibiotic days ranged from 53 to 186 (mean 67.6). In addition, empirical trials of alpha-blockers were unsuccessful. Mean American Urological Association symptom score plus or minus standard deviation was 17.5 +/- 3.7, mean maximum flow rate was 13.3 +/- 4.2 ml. per second, mean detrusor pressure at maximum flow was 46.3 +/- 13.7 cm. water and mean detrusor contraction duration was 132.8 +/- 27.7 seconds. Behavior modification and biofeedback were successful in decreasing symptoms in 35 patients (83%) at 6 months. CONCLUSIONS: These results indicate that some men who are categorized as having and empirically treated for chronic nonbacterial prostatitis are misdiagnosed and, in fact, have functional bladder outlet obstruction. Urodynamics are helpful in diagnosing and predicting success with behavior modification and biofeedback in these patients.

Adult↗

Biological skin covers in treatment of two cases of the Lyell's syndrome.

The treatment of two cases of toxic epidermal necrolysis (Lyell's syndrome) is described. Although some features were common for both ones (young men practically of the same age, reaction after using the same drug) the clinical course of illness was very different. Spontaneous epithelisation of partial-thickness lesions and definitive healing under the xenografts in one patient and full-thickness skin-loss on 12% of body surface with severe septic complications requiring application of cultured keratinocytes and/or skin autografting in the other patient were the main differences. The interdisciplinary approach using a burns treatment protocol in non-burned patient including the close co-operation with the tissue bank in preparing different types of biological covers has been applied.

Adolescent↗

Selective inhibition of interleukin-1 beta gene expression in activated RAW 264.7 macrophages by interferon-gamma.

The ability of interleukin-1 (IL-1) to activate epidermal cell populations supports its role as a key cytokine in the pathogenesis of a number of inflammatory skin diseases. In the present study, we have examined the effect of interferon (IFN)-gamma on the expression of the IL-1 beta gene in mouse RAW 264.7 macrophages activated by lipopolysaccharide (LPS) plus tumor necrosis factor (TNF)-alpha. Incubation of macrophages with both LPS and TNF-alpha resulted in the expression of both IL-1 beta and inducible nitric oxide synthase (iNOS) mRNA transcripts and increased the release of IL-1 beta protein and nitrite production in culture supernatants. Addition of IFN-gamma up-regulated the expression of the iNOS gene in cells activated by LPS + TNF-alpha, but significantly suppressed the induction of IL-1 beta gene expression in a dose-dependent manner. The suppression required neither de novo protein synthesis nor involved destabilization of the mRNA transcripts. Together, these findings suggest that IFN-gamma can be an important regulatory cytokine in a chronic inflammatory site and may explain its purported anti-inflammatory effects in certain dermatological diseases.

Animals↗

Sex differences in absolute rates of bone resorption in young rats: appendicular versus axial bones.

This study compares absolute rates of bone resorption and formation at the organ level in adolescent Sprague-Dawley rats as a function of sex and type of bone. Bone resorption and formation were quantified in rapidly growing male and female rats (4-7 weeks of age) who were multiply prelabeled with [3H]tetracycline. Ten different whole bones were compared: four cranial or appendicular bones and six axial bones. Absolure rate of bone resorption was measured isotopically by the loss of 3H-tetracycline from each whole bone. Bone growth was quantified in terms of relative and absolute increase in bone calcium mass. When the rates of bone resorption (loss of [3H]-tetracycline as percent of whole bone per 3 weeks) were compared between sexes, the six axial bones showed significantly higher rates (P < 0.05-0.001) in males (64-73) than in females (37-66). No significant sex differences were observed in rate for the two cranial and two appendicular bones. During 4-7 weeks of age, a comparison of bone masses showed that only one bone (calvaria) gained more mass in the male and two bones (mandible and humerus) gained more mass in the female. In contrast, five of six axial bones gained more mass in the female. Thus, 7 out of 10 bones were larger in the female. In growing male and female rats, an inverse relationship appears between rate of bone resorption and mass for most of the axial bones; this relationship was not apparent for cranial or appendicular bones. Sexual dimorphism was consistently seen by greater axial bone mass in females. However, greater rates of bone resorption were seen in male axial bones but not in cranial or appendicular bones. It is apparent that the different types of bones are heterogeneous in their rates of resorption and formation during this period of growth.

Animals↗

Previous cesarean delivery and the risk of ectopic pregnancy.

OBJECTIVE: To determine whether previous cesarean delivery is an independent risk factor for ectopic pregnancy. METHODS: We analyzed data collected between October 1988 and August 1990 from a case-control study of ectopic pregnancy among parous, black, non-Hispanic women, 18-44 years old, at a major metropolitan hospital in Georgia. Cases were 138 women with confirmed ectopic pregnancy; controls were 842 women either seeking abortion or delivering an infant. Unconditional logistic regression was used to estimate the relative risk while controlling for the effects of potential confounders selected a priori. RESULTS: Adjusted for age, parity, marital status, history of pelvic inflammatory disease, infertility, douching, and smoking, the odds ratio was 0.6 (95% confidence interval 0.4-1.1), indicating no significant association. CONCLUSION: We found no evidence of an increased risk of ectopic pregnancy related to previous cesarean delivery.

Adolescent↗