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Biomedical subjects

L Gordon

Publications and source records attributed to L Gordon.

At least 37 records · Page 2Linked to original sources
PubMed1999

Treatment of patients with low-grade B-cell lymphoma with the combination of chimeric anti-CD20 monoclonal antibody and CHOP chemotherapy.

PURPOSE: To determine the safety and efficacy of the combination of the chimeric anti-CD20 antibody, Rituxan (Rituximab, IDEC-C2B8; IDEC Pharmaceuticals Corporation, San Diego, CA), and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy. PATIENTS AND METHODS: Forty patients with low-grade or follicular B-cell non-Hodgkin's lymphoma received six infusions of Rituxan (375 mg/m2 per dose) in combination with six doses of CHOP chemotherapy. RESULTS: The overall response rate was 95% (38 of 40 patients). Twenty-two patients experienced a complete response (55%), 16 patients had a partial response (40%), and two patients, who received no treatment, were classified as nonresponders. Medians for duration of response and time to progression had not been reached after a median observation time of 29 + months. Twenty-eight of 38 assessable patients (74%) continued in remission during this median follow-up period. The most frequent adverse events attributable to CHOP were alopecia (38 patients), neutropenia (31 patients), and fever (23 patients). The most frequent events attributed to Rituxan were fever and chills, observed primarily with the first infusion. No quantifiable immune response to the chimeric antibody was detected. In a subset of 18 patients, the bcl-2 [t(14;18)] translocation was positive in eight patients; seven of these patients had complete remissions and converted to polymerase chain reaction (PCR) negativity by completion of therapy. CONCLUSION: This is the first report demonstrating the safety and efficacy of Rituxan anti-CD20 chimeric antibody in combination with standard-dose systemic chemotherapy in the treatment of indolent B-cell lymphoma. The clinical responses suggest an additive therapeutic benefit for the combination with no significant added toxicity. The conversion of bcl-2 from positive to negative by PCR in blood and/or marrow suggests possible clearing of minimal residual disease not previously demonstrated by CHOP chemotherapy alone.

Adult↗
PubMed1999

The usefulness of iodine-123 whole-body scans in evaluating thyroid carcinoma and metastases.

OBJECTIVE: It is recognized that diagnostic doses of (131)I larger than 3 mCi will cause some cell injury to the tissue in which it concentrates and reduce subsequent uptake of (131)I administered therapeutically. Iodine-123 has been suggested as an alternate radiopharmaceutical to perform whole-body scans since its primary emissions are photons with minimal particulate radiation and it does not cause thyroid stunning and cell injury. The purpose of this study was to assess the effectiveness of (123)I for whole-body scans. METHODS: We examined 12 patients who had (123)I whole-body scans for known papillary/follicular thyroid cancer and 1 patient with Hurthle cell carcinoma, all with suspected metastases. All patients had undergone neck surgery and were given 0.81-0 mCi (123)I. Twenty-four hours later a whole-body image and static views of relevant areas were obtained. If abnormal uptake was noted, patients were treated with large doses of (131)I and then had whole-body (131)I scans 7-10 d post-therapy. These images were compared to (123)I whole-body scans. RESULTS: All 13 patients had abnormal (123)I scans and were treated with therapeutic doses of (123)I, followed by whole-body scans 7-10 d later. In 11 patients the activity seen on the 123I scans correlated well with that seen on (131)I scans. In 1 patient, additional lesions were noted on the (131)I images. In another patient, neck activity was seen on the (123)I scan but not on the subsequent (131)I post-therapy scan. The (123)I activity was felt to represent esophageal lumen activity. CONCLUSION: We found (123)1 effective in demonstrating residual thyroid tissue, thyroid carcinoma and metastases, and recommend its use for whole-body iodine scans since it does not cause thyroid stunning.

Bone Neoplasms↗
PubMed1999

Congenital thyroid disease revisited: migrational anomalies and dyshormonogenesis.

Nuclear medicine scintigraphy, in conjunction with other diagnostic tools, plays a vital role in assessing patients with congenital migrational anomalies. We present 5 patients, 4 of whom were hypothyroid and 1 patient who was euthyroid. Scintigraphic and ultrasonographic images were examined and correlated with laboratory results. These patients demonstrate the spectrum of migrational anomalies of the thyroid. Nuclear medicine scintigraphy was a valuable aid in establishing the location of the ectopic thyroid as well as its function.

Adolescent↗
PubMed1998

Identification and characterization of the human homologue of the short PDE4A cAMP-specific phosphodiesterase RD1 (PDE4A1) by analysis of the human HSPDE4A gene locus located at chromosome 19p13.2.

The HSPDE4A gene spans 50 kb, consists of at least 17 exons and is orientated 5'-3', telomere to centromere. It is located at chromosome 19p13.2, being 350 kb proximal to the gene encoding TYK2 and 850 kb distal to the gene encoding the low-density lipoprotein receptor. Its structure is consistent with the production of active 'long' and 'short' isoenzymes as the result of alternative mRNA splicing at two splice junctions. Identified is the single alternatively spliced 5' exon encoding the unique N-terminal region of the long isoenzyme HSPDE4A4B (pde46). The upstream conserved regions, UCR1 and UCR2, which form characteristic domains of PDE4 long forms are each encoded by three exons. The PDE4A-subfamily-specific linker region LR1, which joins UCR1 and UCR2, is encoded by two exons, whereas LR2, which joins UCR2 to the catalytic unit, is encoded by a single exon. Identification of exons encoding an enzymically inactive product of this gene, HSPDE4A8A (2el), indicates that this is an authentic gene product. The 5' exon encoding the unique N-terminal region of the human homologue of the rodent isoform RNPDE4A1A (RD1) was located, and the splice junction used to produce this short PDE4A isoform shown to occur at a different position from that seen in both the rat PDE4B and PDE4D genes. Reverse transcriptase PCR analysis indicates that RD1 homologues are conserved across species, having a conserved membrane-targeting region and a hypervariable LR2 region. Human RD1 was expressed transiently in COS-7 cells and detected as an 83 kDa species primarily associated with the high-speed membrane fraction. Human RD1 exhibited a Km for cAMP of about 3 microM, an IC50 value for inhibition by the PDE4-selective inhibitor rolipram of about 0.3 microM and was considerably more thermostable than rat RD1. Human RD1 was generated as a mature 80 kDa species in an in vitro transcription-translation system and shown to be capable of binding to membranes. Knowledge of the gene structure and the associated sequence information should facilitate analysis of the involvement of PDE4A in hereditary disorders that may result from alterations in enzyme expression, activity, regulation and intracellular targeting and serve as a resource for determining authenticity of cloned PDE4A species.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1998

Fluoxetine treatment of depressive disorders in methadone-maintained opioid addicts.

This study tested the effectiveness of fluoxetine as a treatment for depression in a population of methadone-maintained opioid addicts. Methadone-maintained opioid addicts (44) with depression received fluoxetine or placebo in addition to their methadone, in a double-blind randomized trial, for 12 weeks. Depressive symptoms decreased significantly overall with no significant differences between the groups treated with fluoxetine versus placebo. In addition, drug use outcomes, including cocaine and heroin self-reported use and urine toxicology were measured. There was a significant decrease in heroin use in treatment, but no medication effect. Cocaine use, was unchanged from pre-treatment to endpoint. In separately analyzing data for the subsample of subjects with the most severe depression, there was a significant decrease in depression during treatment and a significant decrease in self-reported cocaine use, but no medication effect on either depressive symptoms or on cocaine use. This study suggests that fluoxetine is not an effective agent in treating depression or cocaine use in this population.

Adult↗
PubMed1998

[A revolutionary Japanese method for treatment of lymphangioma].

Large cystic lymphangiomas of the neck (hygroma colli) have traditionally been treated surgically or by local injection of various sclerosing agents. Owing to the infiltrative growth of these cysts, radical surgery has often been difficult due to the risk of damage to nerves and adjacent organs; and the use of available sclerosing agents has often resulted in disfigurement due to extensive scarring, thus rendering secondary surgery even more difficult. However, OK-432, a new agent for local injection, has been tested with good results, especially in Japan. In five consecutive paediatric cases of lymphangioma, we found ultrasound-guided injection of the cysts with OK-432 to yield good response without complications. In three cases, the lymphangioma disappeared leaving the child's appearance quite normal, and there has been no recurrence. In one case, the lymphangioma disappeared but apparently recurred within half a year (during which time we had lost contact with the family). This was the only case of small cysts (cavernous lymphangioma), which are putatively more resistant to OK-432. The only child to be operated also had thoracic lymphangioma which was not injected, though the cervical part which was injected was reduced by 50 per cent pre-operatively, the final outcome being excellent with no visible cysts in any region. Thus, hitherto our results suggest the therapeutic effect of OK-432 to be good, and further clinical investigation is planned.

Antineoplastic Agents↗
PubMed1998

Regions of sex-specific hypo- and hyper-recombination identified through integration of 180 genetic markers into the metric physical map of human chromosome 19.

The order of and physical distance between 180 polymorphic markers, many from the Généthon and CHLC genetic maps, have been determined through inclusion of probe-positive cosmids in the metric physical map of human chromosome 19. The markers incorporated into the physical map include 38 genetic markers with heterozygosities of > 0.8 and approximately 120 markers with heterozygosities of > 0.60. The average distance between markers in this integrated map is approximately 320 kb. Clustering of markers is noted in several regions of the chromosome; only 11 intervals exist where the distance between markers is greater than 1 Mb, with the largest gap being 1.6 Mb. The ratio of sex-average genetic distance from the Généthon and CHLC genetic linkage maps to physical distance in the metric map is approximately 1.7 cM/Mb for the entire chromosome but ranges from 4 cM/Mb across the telomeric bands to 1 cM/Mb for the centromeric cytogenetic bands. The recombination distance in males is approximately twice that of females in the most telomeric bands but is only 10-25% of the activity observed in females in the more centromeric bands. Seven regions along the chromosome are noted where the recombination distance between markers in one sex is greater than 10 times the recombination distance in the other sex. The integration of genetic markers into the high-resolution physical map of human chromosome 19 provides a framework for isolation of disease genes and resources for studies of genome organization, such as regions of interesting recombinational activity.

Centromere↗
PubMed1998

Adoptive immunotherapy for leukemia: donor lymphocytes transduced with the herpes simplex thymidine kinase gene for remission induction. HGTRI 0103.

This study will evaluate the safety and efficacy of allogenic donor lymphocyte infusions in patients who have relapsed hematologic malignancies after allogeneic bone marrow transplantation (BMT). Donor lymphocyte transfusions have resulted in the cure of some patients with relapsed leukemia or lymphoproliferative disorder after allogeneic BMT, but has been complicated by the development of graft versus host disease (GvHD). We hypothesize that a retroviral vector containing the Herpes simplex thymidine kinase (HStk) gene will allow for retention of the anti-leukemia response of transfused donor lymphocytes while allowing for the adverse effects of GVHD to be mitigated. Patients with relapsed hematologic malignancies after allogeneic BMT will be infused with ex vivo gene modified donor lymphocytes. The Herpes Simplex thymidine kinase (HStk) gene will be transduced into the cells ex vivo using LTKOSN. 1 vector supernate. Insertion of the HStk gene into lymphocytes confers a sensitivity to the anti-herpes drug ganciclovir (GCV). This selective destruction of donor lymphocytes in situ will be used to abrogate the effect of graft versus host disease, if it develops.

Clinical Protocols↗
PubMed1998

Flexor tendon repair using a stainless steel internal anchor. Biomechanical study on human cadaver tendons.

We have developed a stainless steel internal tendon anchor that is used to strengthen a tendon repair. This study tested its use in vitro to produce a repair that can withstand the tensile strength demands of early active flexion. Fresh human cadaver flexor digitorum profundus tendons were harvested, divided, and then repaired using four different techniques: Kessler, Becker or Savage stitches, or the internal tendon anchor. The internal splint repairs demonstrated a 99-270% increase in mean maximal linear tensile strength and a 49-240% increase in mean ultimate tensile strength over the other repairs. It is hoped that this newly developed internal anchor will provide a repair that will be strong enough to allow immediate active range of motion.

Cadaver↗
PubMed1998

Effects of forearm pronation/supination on carpal tunnel pressure.

The effects of forearm rotation and metacarpophalangeal (MP) flexion on carpal tunnel pressure were investigated in 17 healthy adults who had no evidence of carpal tunnel syndrome (CTS). Pressure was continuously recorded with a saline-filled catheter inserted into the carpal tunnel and connected to a pressure transducer while test subjects slowly rotated the forearm from full pronation to full supination. Forearm rotation was repeated with MP flexion of 0 degrees, 45 degrees, and 90 degrees. Both forearm rotation and MP flexion, and their interaction term, significantly affected carpal tunnel pressure and accounted for most of the variability in the data. Highest mean pressures (55 mmHg) were recorded in full supination and 90 degrees MP flexion and lowest pressures (12 mmHg) were recorded at 45 degrees pronation and 45 degrees MP flexion. These data may be useful in the design of tasks and hand tools in the management and prevention of CTS.

Adult↗
PubMed1998

An implantable centrifugal blood pump with a recirculating purge system (Cool-Seal system).

A compact centrifugal blood pump has been developed as an implantable left ventricular assist system. The impeller diameter is 40 mm, and pump dimensions are 55 x 64 mm. This first prototype, fabricated from titanium alloy, resulted in a pump weight of 400 g including a brushless DC motor. The weight of a second prototype pump was reduced to 280 g. The entire blood contacting surface is coated with diamond like carbon (DLC) to improve blood compatibility. Flow rates of over 7 L/min against 100 mm Hg pressure at 2,500 rpm with 9 W total power consumption have been measured. A newly designed mechanical seal with a recirculating purge system (Cool-Seal) is used for the shaft seal. In this seal system, the seal temperature is kept under 40 degrees C to prevent heat denaturation of blood proteins. Purge fluid also cools the pump motor coil and journal bearing. Purge fluid is continuously purified and sterilized by an ultrafiltration unit which is incorporated in the paracorporeal drive console. In vitro experiments with bovine blood demonstrated an acceptably low hemolysis rate (normalized index of hemolysis = 0.005 +/- 0.002 g/100 L). In vivo experiments are currently ongoing using calves. Via left thoracotomy, left ventricular (LV) apex descending aorta bypass was performed utilizing an expanded polytetrafluoroethylene (ePTFE) vascular graft with the pump placed in the left thoracic cavity. In 2 in vivo experiments, the pump flow rate was maintained at 5-9 L/min, and pump power consumption remained stable at 9-10 W. All plasma free Hb levels were measured at less than 15 mg/dl. The seal system has demonstrated good seal capability with negligible purge fluid consumption (<0.5 ml/day). In both calves, the pumps demonstrated trouble free continuous function over 6 month (200 days and 222 days).

Alloys↗
PubMed1998

Total hip replacement rates are higher among Caucasians than Asians in Hawaii.

The etiology of hip osteoarthritis remains unknown but may involve genetic or lifestyle factors. Most cases of total hip replacement are performed because of osteoarthritis. To examine possible ethnic differences, hospital records in Hawaii from 1985 to 1989 were reviewed. Preoperative radiographs were reviewed for a subset of patients to ascertain the reason for total hip replacement. Osteoarthritis accounted for a greater percentage of total hip replacements among whites (59% for women and 66% for men) than among Japanese (36% of women and 30% of men). The incidence of total hip replacement for whites was three to 25 times greater than that of other ethnic groups (Japanese, Chinese, Filipino, and Hawaiians). For example, the risk of total hip replacement for white women 40 years to 84 years of age was 4.4%, compared with 1.1% for Japanese women and 1.7% for Chinese women of the same age group. Compared with published data, the incidence was similar for Chinese in Hawaii and San Francisco; however; whites in Hawaii had a total hip replacement incidence less than half that of whites in San Francisco. Lifestyle differences might account for the lower incidence of total hip replacement for whites in Hawaii, compared with those in San Francisco. The lower incidence among Asians suggests a possible genetic basis for osteoarthritis.

Adult↗
PubMed1997

A murine model of pulmonary damage induced by lipopolysaccharide via intranasal instillation.

This study examines the intranasal instillation of lipopolysaccharide (LPS) into BALB/c mice causing acute pulmonary damage, due to neutrophil infiltration and sepsis. A dose response with LPS showed that an intranasal instillation of 167 microg/ml (10 microg/mouse) caused acute lung injury within 2-4 h and reached maximal damage at 24-48 h. We found the method of LPS administration for induction of acute pulmonary damage to be crucial. After 24 h post-LPS injection, a comparison showed a substantial increase in pulmonary damage with intranasal instillation of LPS. As for intravenous injection, it showed a baseline effect. This study indicates that LPS administered intranasally causes acute pulmonary damage, whereas with intravenous and intraperitoneal endotoxin administration a tissue-specific or similar degree of pulmonary injury may not develop.

Acute Disease↗
PubMed1997

Diamond-Blackfan anaemia: genetic homogeneity for a gene on chromosome 19q13 restricted to 1.8 Mb.

Diamond-Blackfan anaemia (DBA; MIM#205900) is a rare disorder manifested as a pure red-cell aplasia in the neonatal period or in infancy. The clinical hallmark of DBA is a selective decrease in erythroid precursors and anaemia. Other lineages are usually normal and the peripheral white blood cell count is normal. In approximately one-third of cases, the disease is associated with a wide variety of congenital anomalies and malformations. Most cases are sporadic, but 10-20% of them follow a recessive or a dominant inheritance pattern. A female with DBA and a chromosomal translocation involving chromosome 19q was recently identified. We undertook a linkage analysis with chromosome 19 markers in multiplex DBA families of Swedish, French, Dutch, Arabic and Italian origin. Significant linkage to chromosome 19q13 was established for dominant and recessive inherited DBA with a peak lod score at D19S197 (Zmax = 7.08, theta = 0.00). Within this region, a submicroscopic de novo deletion of 3.3 Mb was identified in a patient with DBA. The deletion coincides with the translocation break-point and, together with key recombinations, restricts the DBA gene to a 1.8-Mb region. The results suggest that, despite its clinical heterogeneity, DBA is genetically homogeneous for a gene in 19q13.

Adult↗