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Biomedical subjects

S Furman

Publications and source records attributed to S Furman.

At least 19 recordsLinked to original sources

Vasoactive intestinal peptide and related molecules induce nitrite accumulation in the extracellular milieu of rat cerebral cortical cultures.

Nanomolar concentrations of vasoactive intestinal peptide (VIP), picomolar concentrations of stearyl-norleucine17-VIP (SNV) and femtomolar concentrations of NAPVSIPQ (NAP), an 8-amino-acid peptide derived from the VIP-responsive activity-dependent neuroprotective protein, provide broad neuroprotection. In rat cerebral cortical cultures, 10(-16)-10(-7) M NAP increased intracellular cyclic guanosine monophosphate (cGMP) (2.5-4-fold) and 10(-10) M NAP increased extracellular nitric oxide (NO) by 60%. In the same culture system, VIP and SNV (at micromolar concentrations) increased extracellular NO by 45-55%. The NAP dose required for cGMP increases correlated with the dose providing neuroprotection. However, the concentrations of NAP, SNV and VIP affecting NO production did not match the neuro-protective doses. Thus, NO may mediate part of the cell-cell interaction and natural maintenance activity of VIP/SNV/NAP, while cGMP may mediate neuroprotection.

Animals↗

Calmodulin and profilin coregulate axon outgrowth in Drosophila.

Coordinated regulation of actin cytoskeletal dynamics is critical to growth cone movement. The intracellular molecules calmodulin and profilin actively regulate actin-based motility and participate in the signaling pathways used to steer growth cones. Here we show that in the developing Drosophila embryo, calmodulin and profilin convey complimentary information that is necessary for appropriate growth cone advance. Reducing calmodulin activity by expression of a dominant inhibitor (KA) stalls axon extension of pioneer neurons within the CNS, while a partial loss of profilin function decreases extension of motor axons in the periphery. Yet, surprisingly, when calmodulin and profilin are simultaneously reduced, the ability of both CNS pioneer axons and motor axons to extend beyond the choice points is restored. In the CNS, at the time when growth cones must decide whether to cross or not to cross the midline, a reduction in calmodulin and/or roundabout signaling causes axons to cross the midline inappropriately. These inappropriate crossings are suppressed when profilin activity is simultaneously reduced. Interestingly, the mutual suppression of calmodulin and profilin activity requires a minimal level of profilin. In KA combinations with profilin null alleles, defects in axon extension and midline guidance are synergistically enhanced rather than suppressed. Together, our data indicate that the growth cone must coordinate the activity of both calmodulin and profilin in order to advance past selected choice points, including those dictating midline crossovers.

Actins↗

Feasibility and initial results of an Internet-based pacemaker and ICD pulse generator and lead registry.

The medical community has no independent source of timely information regarding the performance of pacemaker and ICD pulse generators and leads. Accordingly, the authors established an Internet-based registry of pacemaker and ICD pulse generator and lead failures (www.pacerandicregistry.com). During the first year, they found three previously unreported device problems that were promptly communicated to the participants. Of the failures reported, 11% of ICD and 10% of pacemaker pulse generator failures were heralded by signs other than the expected elective replacement indicator (ERI). Average ICD battery longevity was 4.0 +/- 0.7 years, and average dual chamber pacemaker battery longevity was 6.8 +/- 2.6 years. Disrupted insulation accounted for 54% of pacemaker and 29% of ICD lead failures. Compared to pacemaker pulse generator and lead failure, ICD device failures were more likely to cause severe clinical consequences. In conclusion, an Internet-based registry is feasible and capable of providing timely data regarding the signs, causes, and clinical consequences of pacemaker and ICD failures.

Canada↗

The Russ Prize.

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Awards and Prizes↗

Recognition and correction of subcuticular malposition of pacemaker pulse generators.

Implantation of a cardiac pacemaker should be in the tissue plane deep to the subcutaneous tissue (i.e., between the fatty layer and the pectoralis fascia of the chest wall). Five patients with pacemaker implants between the cutis and the subcutaneous fat presented months later with chronic, unremitting, and often excruciating pain. The pulse generator in each case seemed excessively superficial and displaced, appeared too large for its known size, and was seemingly fixed to the overlying skin with exquisite sensitivity to light touch by a garment or palpation. Each had multiple consultations and treatments for pain, all without effect other than the temporary relief of local anesthesia. In three patients with obvious large subcutaneous fatty layers, the pulse generator was markedly superficial. Wound cultures were sterile in each case. Correction consisted of operative repositioning of the pulse generator into the readily developed subcutaneous tissue plane. In each patient, total and permanent relief of pain was achieved. Subcuticular positioning of permanent pacemaker pulse generators causes chronic pain that is readily relieved by operative repositioning of the pulse generator in the proper tissue plane.

Adult↗

A novel peptide prevents death in enriched neuronal cultures.

We have recently cloned a novel protein (activity-dependent neuroprotective protein, ADNP) containing an 8-amino-acid, femtomolar-acting peptide, NAPVSIPQ (NAP). Here we show, for the first time, that NAP exerted a protective effect on glia-depleted neurons in culture. The number of surviving neurons was assessed in cerebral cortical cultures derived from newborn rats. In these cultures, a 24-h treatment with the beta-amyloid peptide (the Alzheimer's disease associated toxin) induced a 30-40% reduction in neuronal survival that was prevented by NAP (10(-13)-10(-11) M). Maximal survival was achieved at NAP concentrations of 10(-12) M. In a second set of experiments, a 5-day incubation period, with NAP added once (at the beginning of the incubation period) exhibited maximal protection at 10(-10) M NAP. In a third set of experiments, a 10-min period of glucose deprivation resulted in a 30-40% neuronal death that was prevented by a 24-h incubation with NAP. Glucose deprivation coupled with beta-amyloid treatment did not increase neuronal death, suggesting a common pathway. We thus conclude, that NAP can prevent neurotoxicity associated with direct action of the beta-amyloid peptide on neurons, perhaps through protection against impaired glucose metabolism.

Alzheimer Disease↗

Recommendations for extraction of chronically implanted transvenous pacing and defibrillator leads: indications, facilities, training. North American Society of Pacing and Electrophysiology Lead Extraction Conference Faculty.

The procedure of lead removal has recently matured into a definable, teachable art with its own specific tools and techniques. It is now time to recognize and formalize the practice of lead removal according to the current methods of medicine and the health care industry. In addition, since at this time the only prospective scientific study of lead extraction is the PLEXES trial, we suggest that studies relating to the techniques of and indications for lead extraction be designed. Recommendations for a common set of definitions, for a framework of training and reviewing physicians in the art, for general methods of reimbursement, and for consistency among clinical trials have been made. Implementation of these recommendations will require additional effort and cooperation from practicing physicians, medical societies, hospital administrations, and industry.

Cardiac Surgical Procedures↗

Experience with the insertion of vena caval filters in acutely burned patients.

The use of inferior vena caval filters in patients at high risk of pulmonary emboli is a standard practice in many types of patients. The usefulness of such filters in acutely burned patients has yet to be established. Twenty inferior vena caval filters were inserted in burn patients. Five were inserted because of preexisting thromboembolic disease. Fifteen were placed prophylactically because of high-risk states, including prolonged immobilization, old age, bleeding problems, and obesity. There were no complications due to filter insertion. No postinsertion emboli were recognized. There were no cases of postinsertion thrombophlebitis. In this small series, the procedure appears to be effective and safe.

Acute Disease↗

Insulation lead failure: is it a matter of insulation coating, venous approach, or both?

Lead insulation material and implant route have a major impact on lead reliability and durability. We compare the incidence of lead insulation failure resulting from both the venous approach and insulation type. Two hundred ninety consecutive leads were followed for a mean period of 57 +/- 30 months; leads with < 1 year follow-up were excluded. There were 116 Silicone Rubber insulated leads and 174 with polyurethane (151 Pellethane 80A and 23 Pellethane 55D) insulation; 279 leads were bipolar and 11 unipolar; 274 leads were implanted in the ventricle and 66 in the atrium. The venous route was the subclavian vein for 170 leads (58%) and the cephalic vein for 120 leads (42%). Insulation failure was diagnosed when a single sign of oversensing, undersensing, failure to capture, early pulse battery depletion, and lead impedance < 250 omega was present. Measurement of lead impedance was performed intraoperatively at implantation and during lead revision or pulse generator replacement. Lead failure caused by conductor coil fracture was not considered. There were 13 lead insulation failures, all among leads with polyurethane insulation (12 Pellethane 80A and 1 Pellethane 55D). Eleven failures (10%) occurred when the subclavian vein and 2 (3%) when the cephalic vein approach was used. The cumulative survival rate of polyurethane and silicone rubber insulated leads was 88.7% and 100%, respectively (P = 0.02); the cumulative survival rate of polyurethane insulated leads was 83.2% when the subclavian vein and 95.1% when the cephalic vein were used (P = 0.03). The mean time to polyurethane lead failure when the subclavian vein approach was used was 54 +/- 17 months and when the cephalic route was 73 +/- 4 months (P < 0.02). By multivariate analysis, the route of entry was found to be a significant variable related to polyurethane insulated lead failure (P < 0.05). At lead revision failure to capture was present in 7, oversensing in 4, and undersensing in 2 instances; impedance was < 250 omega in all cases. Pellethane 80A insulated leads are prone to insulation failure, but more when the subclavian vein is used, rather than the cephalic vein.

Aged↗