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Paul Kurlansky

Publications and source records attributed to Paul Kurlansky.

9 recordsLinked to original sources

Nonmuscle-Invasive Recurrence and Management During Surveillance in Patients with Muscle-Invasive Bladder Cancer Who Achieve Clinical Complete Response to Neoadjuvant Chemotherapy.

PURPOSE: Many patients are medically unfit for or refuse radical cystectomy. Few postchemotherapy bladder-sparing active surveillance programs have reported on nonmuscle-invasive recurrences and treatment outcomes. In this study, we present data on nonmuscle-invasive recurrences and their management in this population. MATERIALS AND METHODS: This is a retrospective review of a prospectively maintained database. All patients received cisplatin-based neoadjuvant chemotherapy and were determined to have a clinical complete response (cCR) based on negative endoscopic resection, urine cytology, and cross-sectional imaging. Patient data were entered into a strict active surveillance protocol. Primary outcomes of interest were number of nonmuscle-invasive recurrences, grade and stage, and treatment. Secondary outcomes of interest were nonmuscle-invasive treatment response rate and muscle-invasive and metastatic recurrence rate. RESULTS: A total of 61 cCR patients were identified. In total, 28 patients experienced a median of 1 nonmuscle-invasive recurrence over a median follow-up of 28.3 months. There were a total of 46 nonmuscle-invasive recurrences, including 9 (20%) low-grade recurrences and 37 (80%) high-grade recurrences. Of the 37 high-grade recurrences, the majority (60%) were treated with Bacillus Calmette-Guérin induction. Nonmuscle-invasive recurrence was not associated with later muscle-invasive recurrence or metastasis. Genomic analysis of paired tumor samples demonstrated clonal relatedness in one patient sample while another sample demonstrated a likely precancerous urothelial field effect. CONCLUSIONS: There is a high rate of nonmuscle-invasive recurrences in patients who achieve cCR to neoadjuvant chemotherapy. However, most of these patients may be safely managed with bladder-preserving treatments. These findings emphasize the importance of vigilant surveillance protocols and appropriate patient selection.

bladder cancer↗

Post-resuscitation reperfusion injury: comparison of periodic Gz acceleration versus Thumper CPR.

The effects of whole body, periodic acceleration (pGz) on cardiopulmonary resuscitation outcome, organ blood flow and tissue inflammatory injury were examined in an experimental pig model, and compared with Thumper (TH)-CPR. VF was induced in 16 pigs, and remained untreated for 3 min, followed by either pGz-CPR or TH-CPR for 15 min. Defibrillation attempts were made at 18 min of VF. Six of eight animals had ROSC in both groups. Post-arrest myocardial dysfunction was present in both groups and progressed over hours. pGz-CPR animals had less wall motion abnormality and higher left ventricular ejection fraction than TH-CPR. The post-resuscitation haemodynamic variables returned to baseline after 3h of ROSC in pGz-CPR group, and remained low in TH-CPR group. The brain blood flow during CPR was similar between TH-CPR and pGz-CPR, 17% and 20% of pre-fibrillation values, respectively. The cardiac blood flow during CPR was significantly lower in pGz-CPR than TH-CPR (TH: 10.2% and pGz: 1.9% of pre-fibrillation value), as well as in other organs. The brain and heart blood flow was significantly higher than pre-fibrillation values after 30 min of ROSC in both groups. The pGz group had significantly higher blood flow in brain, heart and kidney than TH-CPR after 30 min of ROSC. Blood flow in all organs decreased below pre-fibrillation values at 2h of ROSC. Tissue inflammatory injury progressed over hours in the post-resuscitation phase. pGz-CPR group had significantly lower myeloperoxidase (MPO) activity and plasma creatine phosphokinase (CPK) and cardiac troponin I, TNF-alpha, and IL-6 than TH-CPR. Results from the present study demonstrate again that pGz-CPR is an effective method of cardiopulmonary resuscitation, with less post-reperfusion injury compared to TH-CPR.

Acceleration↗

Invited commentary.

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Coronary Artery Bypass↗

Echocardiographic comparison of cardiopulmonary resuscitation (CPR) using periodic acceleration (pGz) versus chest compression.

OBJECTIVE: This investigation compared the effects of conventional cardiopulmonary resuscitation (CPR) using an automated Thumper chest compression device to periodic acceleration CPR (pGz-CPR) on early post-resuscitation ventricular function assessed by echocardiography, in an adult pig model of CPR. BACKGROUND: Whole body periodic acceleration along the spinal axis (pGz) is a new method of cardiopulmonary resuscitation (CPR). Biomechanical forces and biochemical release produced by pGz impart ventilation and increase blood flow. Our laboratory has reported normal neurological and cardiovascular function 48 h after return of spontaneous circulation in animals that have undergone 22 min of pGz-CPR. METHODS: Ventricular fibrillation (VF) was induced in 16 animals (25-35 kg). After 3 min of non-interventional period, the animals were randomized to receive either pGz-CPR or Thumper-CPR for 15 min. After 18 min of VF, a single dose of vasopressin and bicarbonate were administered and defibrillation attempted. An echocardiogram was performed at baseline and serially for 6h. Ejection fraction (EF), fractional shortening (FS) and wall motion were assessed by 2D and M-mode echocardiography. RESULTS: Return of spontaneous circulation to 360 min occurred in 5/8 (62%) of the animals receiving Thumper-CPR and in 7/8 (88%) receiving pGz-CPR. FS and EF were impaired after CPR, but pGz-CPR animals had less impairment than Thumper-CPR animals. Further, wall motion score index (WMSI) was more impaired after Thumper-CPR and remained as such even 6h post-CPR. CONCLUSION: pGz holds promise as a new method for CPR with better left ventricular (LV) function post-CPR than the more traditional chest compression method.

Acceleration↗

Periodic acceleration: effects on vasoactive, fibrinolytic, and coagulation factors.

Cellular and isolated vessel experiments have shown that pulsatile and laminar shear stress to the endothelium produces significant release of mediators into the circulation. Periodic acceleration (pG(z)) applied to the whole body in the direction of the spinal axis adds pulses to the circulation, thereby increasing pulsatile and shear stress to the endothelium that should also cause release of mediators into the circulation. The purpose of this study was to determine whether addition of pulses to the circulation through pG(z) would be sufficient to increase shear stress in whole animals and to acutely release mediators and how such a physical maneuver might affect coagulation factors. Randomized control experiments were performed on anesthetized, supine piglets. The treatment group (pG(z)) (n = 12) received pG(z) with a motion platform that moved them repetitively head to foot at +/-0.4 g at 180 cpm for 60 min. The control group (n = 6) was secured to the platform but remained on conventional ventilation throughout the 4-h protocol. Compared with control animals and baseline, pulsatile stress produced significant increases of serum nitrite, prostacyclin, PGE(2), and tissue plasminogen activator antigen and activity, as well as D-dimer. There were no significant changes in epinephrine, norepinephrine, cortisol, and coagulation factors between groups or from baseline values. Pulsatile and laminar shear stress to the endothelium induced by pG(z) safely produces increases of vasoactive and fibrinolytic activity. pG(z) has potential to achieve mediator-related benefits from the actions of nitric oxide and prostaglandins.

Acceleration↗

Recurrent third-trimester fetal loss and maternal mosaicism for long-QT syndrome.

BACKGROUND: The importance of germ-line mosaicism in genetic disease is probably underestimated, even though recent studies indicate that it may be involved in 10% to 20% of apparently de novo cases of several dominantly inherited genetic diseases. METHODS AND RESULTS: We describe here a case of repeated germ-line transmission of a severe form of long-QT syndrome (LQTS) from an asymptomatic mother with mosaicism for a mutation in the cardiac sodium channel, SCN5A. A male infant was diagnosed with ventricular arrhythmias and cardiac decompensation in utero at 28 weeks and with LQTS after birth, ultimately requiring cardiac transplantation for control of ventricular tachycardia. The mother had no ECG abnormalities, but her only previous pregnancy had ended in stillbirth with evidence of cardiac decompensation at 7 months' gestation. A third pregnancy also ended in stillbirth at 7 months, again with nonimmune fetal hydrops. The surviving infant was found to have a heterozygous mutation in SCN5A (R1623Q), previously reported as a de novo mutation causing neonatal ventricular arrhythmia and LQTS. Initial studies of the mother detected no genetic abnormality, but a sensitive restriction enzyme-based assay identified a small (8% to 10%) percentage of cells harboring the mutation in her blood, skin, and buccal mucosa. Cord blood from the third fetus also harbored the mutant allele, suggesting that all 3 cases of late-term fetal distress resulted from germ-line transfer of the LQTS-associated mutation. CONCLUSIONS: Recurrent late-term fetal loss or sudden infant death can result from unsuspected parental mosaicism for LQTS-associated mutations, with important implications for genetic counseling.

Adult↗

Cardiopulmonary resuscitation (CPR) using periodic acceleration (pGz) in an older porcine model of ventricular fibrillation.

Cardiopulmonary resuscitation (CPR) can be achieved by repetitive motion of the body headwards to footwards in the spinal axis, at 2 Hz and +/- 0.6 G in a juvenile pig model of ventricular fibrillation. Return of spontaneous circulation and normal neurological outcome occurred after a total of 22 min of ventricular fibrillation that included a 3-min noninterventional period [Resuscitation 56 (2003) 215; Resuscitation 51 (2001) 55]. Since older pigs have stiffer rib cages than juvenile pigs and their hemodynamic response to various stimuli might differ, this study was carried out to determine whether this method of CPR, termed pGz-CPR, was just as effective in older pigs. pGz-CPR was also compared to chest compression CPR using an automated mechanical device (CONV-CPR). Ventricular fibrillation was instituted in older pigs weighing 23-34 kg and a 3-min noninterventional period was observed, followed by 15 min pGz-CPR in eight pigs or 15 min CONV-CPR in eight pigs. Return of spontaneous circulation (ROSC) occurred after defibrillation in all eight pigs with pGz-CPR and in six of eight pigs with CONV-CPR. Two of eight pigs with CONV-CPR and none of the eight pigs with pGz-CPR had rib fractures. Hemodynamic instability 15 min after ROSC occurred in all animals with CONV-CPR whereas only three of eight pigs with pGz-CPR demonstrated hemodynamic instability (P < 0.05). We conclude that pGz-CPR in older pigs produces similar ROSC reported by other investigators in pigs without the risk of rib fractures. Further, pGz-CPR is associated with a lower incidence of periods of hemodynamic instability following ROSC than CONV-CPR.

Acceleration↗

Survival and normal neurological outcome after CPR with periodic Gz acceleration and vasopressin.

BACKGROUND: We showed previously that whole body periodic acceleration along the spinal axis (pGz) is a novel method of cardiopulmonary resuscitation (CPR). The ultimate assessment of the value of any CPR technique is the neurological outcome after using such a technique. In this study, we determined the neurological outcome in pigs after prolonged pGz-CPR, with administration of vasopressin immediately prior to defibrillation. Neurological outcome after pGz-CPR was compared to a control group where no intervention occurred for the same time period (C-NoInterv). METHODS AND RESULTS: Ventricular Fibrillation (VFIB) was induced in 12 animals. After a 3 min non-interventional interval, the animals received either pGz-CPR (n=7), or C-NoInterv (n=5) for 15 min. After 18 min of VFIB, a single dose of vasopressin (0.8 U/kg) was administered along with sodium bicarbonate and bretylium, and defibrillation was attempted. All animals in the pGz-CPR group had return of spontaneous circulation (ROSC) and normal neurological assessment at 24 h. Neurologic outcome remained normal at 48 h. In contrast, none of the animals in the C-NoInterv had ROSC. CONCLUSION: Prolonged pGz-CPR, with administration of vasopressin immediately prior to defibrillation results in normal neurological outcomes at 24 h.

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Impact of community-wide police car deployment of automated external defibrillators on survival from out-of-hospital cardiac arrest.

BACKGROUND: Disappointing survival rates from out-of-hospital cardiac arrests encourage strategies for faster defibrillation, such as use of automated external defibrillators (AEDs) by nonconventional responders. METHODS AND RESULTS: AEDs were provided to all Miami-Dade County, Florida, police. AED-equipped police (P-AED) and conventional emergency medical rescue (EMS) responders are simultaneously deployed to possible cardiac arrests. Times from 9-1-1 contact to the scene were compared for P-AED and concurrently deployed EMS, and both were compared with historical EMS experience. Survival with P-AED was compared with outcomes when EMS was the sole responder. Among 420 paired dispatches of P-AED and EMS, the mean+/-SD P-AED time from 9-1-1 call to arrival at the scene was 6.16+/-4.27 minutes, compared with 7.56+/-3.60 minutes for EMS (P<0.001). Police arrived first to 56% of the calls. The time to first responder arrival among P-AED and EMS was 4.88+/-2.88 minutes (P<0.001), compared with a historical response time of 7.64+/-3.66 minutes when EMS was the sole responder. A 17.2% survival rate was observed for victims with ventricular fibrillation or pulseless ventricular tachycardia (VT/VF), compared with 9.0% for standard EMS before P-AED implementation (P=0.047). However, VT/VF benefit was diluted by the observation that 61% of the initial rhythms were nonshockable, reducing the absolute survival benefit among the total study population to 1.6% (P-AED, 7.6%; EMS, 6.0%). CONCLUSIONS: P-AED establishes a layer of responders that generate improved response times and survival from VT/VF. There was no benefit for victims with nonshockable rhythms.

Aged↗