Genentech stands by original data.
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Biotechnology↗
Biomedical subjects
M Ross
Publications and source records attributed to M Ross.
Organophosphate skin decontamination using immobilized enzymes.
We previously demonstrated that a combination of cholinesterase (ChE) pre-treatment with an oxime is an effective measure against soman and sarin. We describe here a novel approach for the preparation of covalently linked ChEs which are immobilized to a polyurethane matrix. Such preparation of ChE-sponges enhances the stability and usefulness of the enzymes in non-physiological environments. The ChE-sponges, which can be molded to any form, can effectively be used to remove and decontaminate organophosphates (OPs) from surfaces, biological (skin or wounds) or otherwise (clothing or sensitive medical equipment), or the environment. The ChE-sponges retained their catalytic activity under conditions of temperature, time, and drying where the native soluble enzyme would rapidly denature, and can be reused in conjunction with oximes many times. The ChE-sponge in the presence of oxime repeatedly detoxified OPs such as DFP or MEPQ. These developments in ChE technology have extended the applicability of OP scavengers from in vivo protection, to a variety of external detoxification and decontamination schemes. In addition to treatment of OP-contaminated soldiers, the ChE-sponge could protect medical personnel from secondary contamination while attending chemical casualties, and civilians exposed to pesticides or highly toxic nerve agents such as sarin.
Cholinesterase Inhibitors↗
Mounting a defence against Alzheimer's disease.
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Alzheimer Disease↗
Phase II studies with DaunoXome in patients with nonresectable hepatocellular carcinoma: clinical and pharmacokinetic outcomes.
A total of 14 Chinese patients with inoperable hepatocellular carcinoma received a liposomal formulation of daunorubicin (DaunoXome) at a dose equivalent to 100 mg/m2 of the free drug every 3 weeks. Altogether, 12 patients were assessable for response; 2 patients had stable disease for 8 weeks, but all eventually developed progressive disease and there was no responder. The drug was well tolerated, with no evidence of cardiac toxicity being observed. Deterioration of liver-function tests was attributed to progressive tumors in the terminal stage of the disease. Pharmacokinetics studies revealed a biexponential decay for daunorubicin in association with mean initial and terminal half-lives of 1.8 and 7.4 h, respectively, and a mean total clearance of 15.0+/-5.5 ml/min. The AUC ratio between the metabolite daunorubicinol and daunorubicin was 0.07. These data differ markedly from the pharmacokinetics of the free drug.
Adult↗
Cervical electromyographic activity during low-speed rear impact.
Whiplash motion of the neck is characterized by having an extension-flexion motion of the neck. It has been previously assumed that muscles do not play a role in the injury. Eight healthy males were seated in a car seat mounted on a sled. The sled was accelerated by a spring mechanism. Muscle electromyographic (EMG) activity was measured by wire electrodes in semi-spinalis capitis, splenius capitis, and levator scapulae. Surface EMG activity was measured over trapezius and sternocleidomastoideus. Wavelet analysis was used to establish the onset of muscle activity with respect to sled movement. Shorter reaction times were found to be as low as 13.2 ms from head acceleration and 65.6 ms from sled acceleration. Thus the muscles could influence the injury pattern. It is of interest that clinical symptoms are often attributed to muscle tendon injuries.
Acceleration↗
Cyclosporine, methotrexate, and prednisone compared with cyclosporine and prednisone for prevention of acute graft-vs.-host disease: effect on chronic graft-vs.-host disease and long-term survival.
Graft-vs.-host disease (GVHD) is a major predictor of outcome following allogeneic bone marrow transplantation (BMT). For patients alive at day 100 after BMT, the presence or absence of chronic GVHD is one of the most important determinants of survival and quality of life. We wished to determine the effects on chronic GVHD of two regimens used for the prophylaxis of acute GVHD: cyclosporine, methotrexate, and prednisone (CSA/MTX/PSE) and cyclosporine and prednisone (CSA/PSE). One hundred forty-nine evaluable patients were entered into the acute GVHD study. As of 31 March 1997, 63 months after the last patient underwent BMT, the median survival time was 4.5 years (range 0.09-9.9). The incidence of chronic GVHD was independent of the prophylactic regimen (55 vs. 54%), and extensive chronic GVHD occurred in 25 and 24% of patients receiving CSA/MTX/PSE and CSA/PSE, respectively. Of note, the median Karnofsky performance status of both groups was 100% (range 70-100%), reflecting the low incidence of extensive chronic GVHD. Survival rates free of chronic GVHD were 52 vs. 42% (p = 0.29) for patients receiving CSA/MTX/PSE vs. CSA/PSE. The incidence of relapse was also similar in both groups of patients. These data suggest that the combinations of CSA/MTX/PSE and CSA/PSE result in comparable chronic GVHD-free survival without an increase in leukemic relapse.
Acute Disease↗
Post-mortem incidental finding of cytomegalovirus oophoritis after an allogeneic stem cell transplant.
Cytomegalovirus (CMV) disease is a common and serious complication of allogeneic stem cell transplantation (SCT). Its two most frequent manifestations are interstitial pneumonitis and gastroenteritis. We describe here the first reported case of CMV ovarian infection in an allo-SCT recipient. This patient was included in a clinical trial of high-dose chemotherapy (HDCT) with HLA-matched peripheral SCT for metastatic breast cancer. She expired 53 days after transplantation from organ failure unrelated to her CMV oophoritis.
Antineoplastic Combined Chemotherapy Protocols↗
High-dose therapy with autologous hematopoietic cell support as salvage treatment for patients with breast cancer who have relapsed after previous high-dose chemotherapy.
Twenty-six patients with breast cancer who had relapsed after previously receiving high-dose chemotherapy and autologous hematopoietic cell support received a second course of high-dose cytoreductive therapy and autologous hematopoietic cell support as salvage therapy. Several different high-dose therapy regimens were employed for the second transplant, including a radiolabeled immunoconjugate. Two patients died of treatment-related complications. The remaining 24 patients relapsed a median of 126 (range 22-635) days after salvage transplant. All have since died. The median survival after salvage transplant was 362 (range 31-931) days. We conclude that second courses of high-dose therapy as salvage treatment are generally well-tolerated but their efficacy is modest. Alternative treatment strategies are needed for these patients.
Adult↗
Breath-hold 3D MR angiography of the renal vasculature using a contrast-enhanced multiecho gradient-echo technique.
OBJECTIVE: Significant evolution of contrast-enhanced MR angiography for evaluating vascular diseases in the abdomen has occurred during the past several years. The state-of-the-art gradient-echo imaging technique employs a short echo time (TE) and a short repetition time (TR) for rapid vascular imaging with contrast-enhanced MR angiography. However, because of the short TR (< or = 3-8 msec), the background stationary tissue becomes saturated, with resultant poor contrast resolution of visceral organs. The authors present a new approach to vascular imaging using a multiecho gradient-echo technique with a TR sufficiently long (41 msec) to image the renal vasculature and parenchyma without background tissue suppression. METHODS: Twenty-four partitions (3D slab thickness = 72 mm) with an in-plane resolution of 224 x 256 were obtained in 21 seconds. Three measurements were performed with an interscan delay of 8 seconds. In the pulse sequence, the partition loop is defined as the innermost loop, in which Kz views are acquired centrically for a fixed Ky, followed by Ky views in a conventional linear or sequential order. The partition encodings are segmented to permit multiple encodings in which two TR loops were used to span a total of 24 echoes with 12 along the positive and 12 along the negative direction in k space. A large bandwidth of 650 Hz/pixel was used to keep the echo train length short, with an echo spacing of 1.86 msec. A frequency-selective fat saturation pulse was placed before slab-selective excitation. The other parameters in the pulse sequence were TR/TE/flip = 41/2.2/45; the field of view was 360 to 390 mm. Maximum intensity projections of each 3D contrast-enhanced measurement were performed. The vascular-to-background contrast, bowel-related magnetic susceptibility artifact, and background stationary signals were subjectively graded. The authors examined the utility of this technique in 16 randomly selected patients (3 normal, 13 abnormal) with varied renal vasculature and parenchymal abnormalities. Results were confirmed with conventional x-ray angiography, surgery, or clinical follow-up. RESULTS: Vascular-to-background contrast was graded as very good (grade III/III) in all cases. The bowel-related magnetic susceptibility artifacts were not considered significant. Background visceral organ soft tissue contrast was not suppressed and was graded as good (grade III/III) in all cases. Eight hemodynamically significant (> 50% diameter) stenoses in seven patients were accurately assessed (one with fibromuscular dysplasia). Three patients with renal masses (two with renal cell carcinoma and one with renal lymphoma) were accurately assessed for arterial anatomy and venous extension. Other renal venous abnormalities seen were retroaortic renal vein (n = 1), chronic occlusion (n = 1), and accessories (total of five) (n = 1). CONCLUSIONS: Rapid breath-hold contrast-enhanced MR angiography of the renal vasculature with a multiecho gradient-echo using a long TR depicted the renal vasculature with high vessel-to-background contrast without significant bowel-related susceptibility artifact and without background visceral organ tissue signal suppression, resulting in high background soft tissue contrast resolution.
Artifacts↗
Sale of sex for drugs and drugs for sex: an economic context of sexual risk behavior for STDs.
BACKGROUND AND OBJECTIVES: Persons who participate in behaviors such as drug use and buying or selling sex are at elevated risk for sexually transmitted diseases (STD)/human immunodeficiency virus (HIV) infection. GOALS: To describe the economic structure supporting drug use and the buying and selling of sex services in two urban Houston communities. STUDY DESIGN: Residents of two Houston communities participated in street-intercept interviews to obtain information on sex and drug use behaviors. RESULTS: Many members of the population reported having bought or sold sex. A history of crack use significantly predicted the trading of sex for money and drugs, and sellers of sex were more likely to have engaged in recent high-risk sexual behavior than those who had never sold sex. CONCLUSION: The data are suggestive of an underground economy for the exchange of sex for drugs or money, the existence of which facilitates the spread of STDs in high-risk communities.
Adult↗
The role of private physicians in STD control in two inner-city communities in Houston, Texas.
Although sexually transmitted diseases (STDs) are particularly widespread in poor, largely minority, inner-city areas, little is known about the role private physicians play in these communities in STD control. A cross-sectional mail survey of private physicians potentially involved in STD management in two inner-city communities in Houston, Texas with STD prevalence rates well above city, state, and national averages was conducted to find the level and type of STD care provided. Twenty-seven of 65 physicians completed the survey. The survey found that the preventive orientation among private providers of medical care in these inner-city communities has to be increased to effectively control STDs.
Cross-Sectional Studies↗
Factors controlling the expression of 5alpha-reductase in human prostate: A possible new approach for the treatment of prostate cancer.
The functional activity of the 5alpha-reductase isoenzyme in the human prostate is gradually depleted as the gland undergoes transformation from the normal to the metastatic state. There are two isoforms of this enzyme expressed in the prostate and recent studies have demonstrated that the type II isoenzyme is the one most affected by the onset of neoplasia. To elucidate the mechanism(s) responsible for the down-regulation of the isoenzyme activity, we re-examined the nature of the interaction between stroma and epithelial cells in the human prostate. We noted that the control of the isoenzyme expression in the epithelial cells was regulated by a paracrine factor specific to the prostate fibroblast. In the absence of this factor the human prostate loses its capacity to express the 5alpha-reductase type II isoenzyme - a characteristic manifested simultaneously with the loss of differentiation in the tissues. This finding presents a totally new concept to the control of 5alpha-reductase in the human prostate and offers a possibility for an interesting and alternative approach to the management of prostate cancer.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
Prognostic and predictive factors for patients with metastatic breast cancer undergoing aggressive induction therapy followed by high-dose chemotherapy with autologous stem-cell support.
PURPOSE: We performed a retrospective review to determine predictive and prognostic factors in patients with metastatic breast cancer who received induction therapy, and, if they responded to treatment, high-dose chemotherapy. PATIENTS AND METHODS: Patients with metastatic breast cancer received induction therapy with doxorubicin, fluorouracil, and methotrexate (AFM). Partial responders then received immediate high-dose chemotherapy, whereas those who achieved complete remission were randomized to immediate or delayed high-dose chemotherapy with hematopoietic stem-cell support. We performed a retrospective review of data from these patients and used Cox proportional hazards regression models for analyses. RESULTS: The overall response rate for the 425 patients enrolled was 74% (95% confidence interval, 70% to 78%). Multivariate analysis of data from all 425 patients revealed that positive estrogen receptor status (P =.0041), smaller metastatic foci (</= 2 v > 2 cm) (P =. 0165), a longer disease-free interval from initial diagnosis to diagnosis of metastases (</= 2 v > 2 years) (P =.0051), and prior treatment with tamoxifen (P =.0152) were good prognostic signs for overall survival. Patients who had received prior adjuvant therapy (P =.0001) and those who developed liver metastases (P =.0001) had decreased long-term survival. In the subgroup of responders to AFM induction, multivariate analysis showed that those with visceral metastases did less well (P =.0006), as did patients who had received prior adjuvant therapy (P =.0023). However, those who had received tamoxifen therapy in the adjuvant setting did better (P =. 0143). CONCLUSION: The chance for long-term remission with induction therapy with AFM and high-dose chemotherapy is increased for hormone receptor positive-patients with nonvisceral metastases who have not received prior adjuvant chemotherapy and have long disease-free intervals.
Adult↗
Preventing syphilis: lessons from a survey of two inner-city communities in Houston, Texas.
To develop a relevant, community-based prevention campaign, the authors examined, using street-intercept interviews, syphilis-related knowledge, circulation of information, and screening and treatment practices among four hundred residents of two inner-city communities in Houston, Texas, where syphilis case rates exceed city, county, and national averages. Although awareness of syphilis was near universal, one-fourth of the respondents thought syphilis was incurable, and a large proportion confused syphilis with other sexually transmitted diseases (STDs), mentioning discharge and burning or itching in the genital area as symptoms. Almost four out of five respondents were aware of free treatment and screening facilities in the local area, yet, less than two of five expressed the intention to get tested within the next month. Only 22 percent had seen or heard anything about syphilis in the past twelve months. The resultant prevention campaign is discussed along with implications for the development of comprehensive STD prevention and control campaigns in similar poor and underserved communities.
Adolescent↗
The palmomental reflex elicitation by electrical stimulation of the median nerve.
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Action Potentials↗
Ibuprofen-induced inhibition of cyclooxygenase isoform gene expression and regression of rat mammary carcinomas.
A single dose of 75 mg/kg 7,12 dimethylbenz[a]anthracene was administered to 50-day-old virgin female Sprague-Dawley rats and 100 days later, animals were randomized and provided with Teklad rodent chow mixed with a dose of 25 mg/rat/day ibuprofen for 35 days. Ibuprofen treatment reduced tumor volume (P < 0.05) and significantly inhibited gene expression of both cyclooxygenase- and cyclooxygenase-2 (P < 0.02). These results indicate that ibuprofen induced significant regression of established mammary carcinomas which was associated with inhibition of expression of isoforms of the gene responsible for prostaglandin production.
9,10-Dimethyl-1,2-benzanthracene↗
Neuromuscular propagation after fatiguing contractions of the paralyzed soleus muscle in humans.
We analyzed the M wave and torque after repetitive activation and recovery of the human soleus muscle in individuals with spinal cord injury. Fifteen individuals with complete paralysis had the tibial nerve activated for 330 ms every second with a 20-Hz train. The M wave and torque were analyzed before fatigue, immediately after fatigue, and during recovery. The torque and three M-wave measurements (amplitude, duration, median frequency) changed significantly after fatigue in the chronic group, but the M-wave area was not changed. The M wave was completely recovered after 5 min of rest, even though the torque remained depressed during recovery. The M-wave changes appeared to contribute minimally to the reduced torque in individuals with chronic paralysis. The disassociation in the M-wave-torque relationship during fatigue and recovery suggests, that electrical stimulation under electromyography control is not an ideal method to optimize torque in paralyzed muscle.
Adult↗
Gene therapy with AdV-IL2 (TG 1021) in unresectable digestive adenocarcinoma. Phase I-II study, first inclusions.
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Adenocarcinoma↗