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Biomedical subjects

S C Stein

Publications and source records attributed to S C Stein.

At least 19 recordsLinked to original sources

Brief history of surgical timing: surgery for ruptured intracranial aneurysms.

The neurosurgical profession has taken a circuitous route to attain its current knowledge about timing for aneurysm surgery. While addressing the timing issue, neurosurgeons were beset by many pressures simultaneously. They were forced to justify not only optimal surgical techniques but the need for surgery at all in the treatment of ruptured aneurysms. The beliefs of surgeons with strong personalities, in addition to intuitive guesses, often served to guide surgery in the absence of scientific evidence. That any progress could be made against a background of desperately ill patients and frustrating early results is remarkable. The author briefly outlines the controversies and misdirection that accompanied this progress toward understanding surgical timing in the treatment of ruptured aneurysms.

Aneurysm, Ruptured↗

The regulation of AMP-activated protein kinase by phosphorylation.

The AMP-activated protein kinase (AMPK) cascade is activated by an increase in the AMP/ATP ratio within the cell. AMPK is regulated allosterically by AMP and by reversible phosphorylation. Threonine-172 within the catalytic subunit (alpha) of AMPK (Thr(172)) was identified as the major site phosphorylated by the AMP-activated protein kinase kinase (AMPKK) in vitro. We have used site-directed mutagenesis to study the role of phosphorylation of Thr(172) on AMPK activity. Mutation of Thr(172) to an aspartic acid residue (T172D) in either alpha1 or alpha2 resulted in a kinase complex with approx. 50% the activity of the corresponding wild-type complex. The activity of wild-type AMPK decreased by greater than 90% following treatment with protein phosphatases, whereas the activity of the T172D mutant complex fell by only 10-15%. Mutation of Thr(172) to an alanine residue (T172A) almost completely abolished kinase activity. These results indicate that phosphorylation of Thr(172) accounts for most of the activation by AMPKK, but that other sites are involved. In support of this we have shown that AMPKK phosphorylates at least two other sites on the alpha subunit and one site on the beta subunit. Furthermore, we provide evidence that phosphorylation of Thr(172) may be involved in the sensitivity of the AMPK complex to AMP.

AMP-Activated Protein Kinase Kinases↗

Rand-Stein analgesia protocol for cataract surgery.

OBJECTIVE: To describe the safety and efficacy of an analgesia protocol that enables the surgeon to maintain control over an alert patient experiencing seemingly painless ambulatory cataract surgery, while eliminating the risks and side effects associated with general, local, topical, and intracameral anesthesia. DESIGN: Noncomparative, interventional case series. PARTICIPANTS: Five thousand one hundred sixty-eight consecutive cataract surgery cases operated on by the same surgeon from April 1, 1993 through June 1, 1998. METHODS: This technique produces profound ocular analgesia, avoiding any undesired sedative effects, using very low-dose, titrated, intravenous alfentanil. Complete control of the uncooperative patient, including lid squeezing and ocular and general body movements, is obtainable whenever necessary using very low-dose, titrated, intravenous methohexital. MAIN OUTCOME MEASURES: Success was defined as surgery completed in a controlled manner without the need to convert to general, local, topical, or intracameral anesthesia and the patient's experience being perceived as pain free. RESULTS: One hundred percent of the cases were successful without ever deviating from the protocol. CONCLUSIONS: This analgesia protocol offers advantages for cataract surgery. It virtually eliminates the morbidity of cataract surgery associated with other anesthesia techniques while providing excellent and reliable control. It allows for an immediate postoperative recovery with instantaneous vision restoration. These patients are generally awake, alert, and retain their protective reflexes.

Adolescent↗

Characterization of the role of AMP-activated protein kinase in the regulation of glucose-activated gene expression using constitutively active and dominant negative forms of the kinase.

In the liver, glucose induces the expression of a number of genes involved in glucose and lipid metabolism, e.g., those encoding L-type pyruvate kinase and fatty acid synthase. Recent evidence has indicated a role for the AMP-activated protein kinase (AMPK) in the inhibition of glucose-activated gene expression in hepatocytes. It remains unclear, however, whether AMPK is involved in the glucose induction of these genes. In order to study further the role of AMPK in regulating gene expression, we have generated two mutant forms of AMPK. One of these (alpha1(312)) acts as a constitutively active kinase, while the other (alpha1DN) acts as a dominant negative inhibitor of endogenous AMPK. We have used adenovirus-mediated gene transfer to express these mutants in primary rat hepatocytes in culture in order to determine their effect on AMPK activity and the transcription of glucose-activated genes. Expression of alpha1(312) increased AMPK activity in hepatocytes and blocked completely the induction of a number of glucose-activated genes in response to 25 mM glucose. This effect is similar to that observed following activation of AMPK by 5-amino-imidazolecarboxamide riboside. Expression of alpha1DN markedly inhibited both basal and stimulated activity of endogenous AMPK but had no effect on the transcription of glucose-activated genes. Our results suggest that AMPK is involved in the inhibition of glucose-activated gene expression but not in the induction pathway. This study demonstrates that the two mutants we have described will provide valuable tools for studying the wider physiological role of AMPK.

AMP-Activated Protein Kinases↗

Laminectomy compared with laparoscopic diskectomy and outpatient laparoscopic diskectomy for herniated L5-S1 intervertebral disks.

The objective of this study was to evaluate the clinical efficacy and cost effectiveness of inpatient and outpatient laparoscopic lumbar diskectomy (LLD) compared with laminectomy (LAM) in the surgical treatment of disabling L5-S1 disk herniation. Sixty-two adults underwent surgery for herniated L5-S1 intervertebral disks (31 LLD and 31 LAM). Operative blood loss (EBL) (milliliters), operative time (ORT) (minutes), hospital stay (LOS), and rehabilitation time to normal activity (REHAB) (days), recurrent symptoms, postoperative morbidity, percent pain free, and hospital patient charges were calculated. Thirty LLD patients (97%) had immediate relief of disk pain. Morbidity after LLD included transient urinary retention (one) and rectus hematoma (one). One LAM patient had a pseudomeningocele. Among patients observed for > or =6 months, with a median follow up time of 34 months, 22 of 25 LLD patients (88%) returned to normal activity, while 12 of the LAM group (52%) were disabled (p = 0.004). Functional outcome was improved by LLD for workers compensation patients followed > or =6 months, with 86% LAM disabled, vs. 10% LLD (p = 0.001). Sixteen LLD patients (52%) and 18 (58%) of the LAM group needed postoperative physical therapy. Four LLD patients recurred; three required reoperation. Four LAM patients had surgery for recurrent disk herniation. ORT was longer for LLD than LAM (210 vs. 158 minutes, median, p < 0.05). EBL and REHAB time were significantly reduced with LLD, vs. LAM. With a median follow-up of 34 months, 58% of LLD and 39% of LAM patients followed > or =6 months were pain free. Outpatient LLD (n = 9) reduced LOS (1 day vs. 2 days and 4 days, p < 0.01) and lowered patient charges ($4,405 vs. $5,723 and $7,192, p < 0.01) compared with inpatient LLD (n = 23) and LAM, respectively. LLD is a safe, cost-effective, minimally invasive alternative to LAM for treating herniated L5-S1 disks. Compared with LAM, LLD reduces EBL, LOS, REHAB time, and patient charges, improves function, and increases long-term pain relief. Cost effectiveness is optimized when LLD is performed as outpatient surgery.

Adult↗

Laparoscopic L5-S1 diskectomy: a cost-effective, minimally invasive general surgery--neurosurgery team alternative to laminectomy.

Laparoscopic L5-S1 diskectomy (LLD) is a promising new technique for managing disabling pain from herniated lumbar disks. It is unknown, however, whether the clinical results of LLD are superior to those of traditional laminectomy (LAM). This study was undertaken, therefore, in order to compare LLD and LAM in the management of L5-S1 disk herniation unresponsive to conservative treatment measures. Clinical records of 22 patients who underwent 23 LLD procedures and of 23 LAM patients were reviewed with respect to demographics and median age, operative blood loss, operative time, hospital stay, and time of rehabilitation to work/normal activity, as well as postoperative morbidity, recurrent symptoms, long-term functional status, and inhospital patient charges. Two LLD patients had undergone LAM previously, and one had a percutaneous microdiskectomy. All LLD patients had relief of disk pain immediately after surgery. Morbidity after LLD included transient brachial plexus neuropraxia (1), urinary retention (1), and rectus hematoma (1). No LAM complications were reported. Among LLD patients, compared with LAM, median age (34.5 years versus 40 years), estimated blood loss (12 mL versus 68 mL), hospital length of stay (1 day versus 3 days), time to normal activity (17 days versus 79 days) and mean inhospital patient charges ($5,737 +/- 283 versus $7,762 +/- 662) were reduced significantly (P < 0.05). LLD operating time was significantly longer than LAM (210 versus 160 minutes median, P < 0.01). With a median follow-up time of 11.0 months (range, 2 to 23 months) all LLD patients had returned to normal activity, whereas 7 of the LAM group (30%) remained disabled (P < 0.01). Sixty-eight per cent of LLD patients were pain-free during follow-up, compared with 39 per cent of the LAM group (P < 0.05). Sixty-four per cent of LLD patients and 57 per cent of the LAM group needed postoperatively physical therapy. One LLD and 4 LAM patients required reoperation, by LLD and LAM, respectively, for recurrent disk herniation. LLD is a safe, cost-effective, minimally invasive operation for managing disabling L5-S1 disk herniation. Compared with LAM, LLD reduces blood loss, length of stay, rehabilitation time, and patient charges, and improves long-term functional and pain-free status. LLD should be considered as an alternative to LAM for patients with herniated L5-S1 intervertebral disks unresponsive to conservative management.

Adult↗

Laparoscopic laser lumbar diskectomy. Operative technique and case report.

Approximately 300,000 patients each year in the United States undergo laminectomy for disabling lumbar disc herniation. Post-laminectomy hospitalization is 3-7 days and convalescence may be prolonged. As an alternative to laminectomy, we have developed a technique for performing L5-S1 lumbar diskectomy laparoscopically. Using an anterior approach, the intervertebral disc space is opened and the diskectomy is performed under direct videolaparoscopic imaging. After pneumoperitoneum is established, the patient is placed in a steep Trendelenburg position. The small bowel is retracted cephalad and the colon is moved to the left. The iliac vessels are identified visually and by Doppler probe, and the presacral space is dissected in the midline to expose the L5-S1 disc. In the case presented, the disc annulus was opened with the Nd:YAG contact laser, and diskectomy was performed under direct videolaparoscopic vision using standard neurosurgical instruments modified for laparoscopy. The posterior longitudinal ligament can be visualized directly to define the posterior limits of the completed diskectomy. In the case described, pain relief was confirmed immediately after the procedure. The patient was discharged after 2 hospital days, and returned to normal activity in 8 days.

Adult↗

Delayed and progressive brain injury in children and adolescents with head trauma.

We performed serial CT scans on 351 children and adolescents with serious closed-head injury. Delayed or progressive lesions were encountered in 145 (41%). The occurrence of such delayed cerebral injuries correlated with the severity of the initial head trauma, with the presence of major extracranial injury and with studies of coagulopathy on admission. The presence of delayed cerebral injury had a profound influence on survival and recovery from head trauma, especially when the initial severity of the head injury was taken into account. We conclude that serial CT scans provide a reliable means of diagnosing and following the progress of delayed cerebral injury in the pediatric population.

Adolescent↗

The Head Injury Severity Scale (HISS): a practical classification of closed-head injury.

The authors introduce a two-dimensional scale for rating closed-head injury, the Head Injury Severity Scale (HISS). This system is based on a five-interval severity classification (minimal through critical), determined primarily by the initial post-resuscitation Glasgow Coma Scale score. The second dimension is predicated on the presence or absence of complications, appropriate for each severity interval. The outcomes of almost 25,000 patients with head injury encountered at our institution over a 7-year period were evaluated. We discovered that adding a complication dimension to each severity category resulted in significant outcome differences and effectively divided patients into groups with very different risks, prognosis and treatment requirements. The HISS is proposed as a framework on which further research can be done to guide care to predict outcome and to perform audits on head-injured patients.

Brain Damage, Chronic↗

Laparoscopic lumbar diskectomy: preliminary report of a minimally invasive anterior approach to the herniated L5-S1 disk.

Approximately 300,000 patients each year in the United States undergo laminectomy for disabling lumbar disk herniation. Postlaminectomy hospitalization is 3-7 days and convalescence may be prolonged. As an alternative to laminectomy, we have developed a technique for performing L5-S1 lumbar diskectomy laparoscopically. Using an anterior approach, the intervertebral disk space is opened and the diskectomy is performed under direct videolaparoscopic imaging. After pneumoperitoneum is established, the patient is placed in a steep Trendelenburg position. The small bowel is retracted cephalad and the colon moved to the left. The iliac vessels are identified visually and by Doppler probe. Then the presacral space is dissected in the midline to expose the L5-S1 disk. The disk annulus is opened with the Nd:YAG contact laser (four cases) or the harmonic scalpel (three cases). Diskectomy is performed under direct videolaparoscopic vision using standard neurosurgical instruments modified for laparoscopy. The posterior longitudinal ligament can be visualized directly to define the posterior limits of the completed diskectomy. Laparoscopy lumbar diskectomy has been performed on seven patients (five male, two female). No perioperative complications occurred. All seven patients had immediate relief of back pain after laparoscopic lumbar diskectomy. Five patients were discharged the next day and two on the second postoperative day. L5-S1 laparoscopic lumbar diskectomy is feasible and safe. It may be an effective minimally invasive alternative to laminectomy.

Adult↗

Delayed and progressive brain injury in closed-head trauma: radiological demonstration.

The importance of delayed or secondary brain insults in the eventual outcome of closed-head trauma has been documented in experimental models. To understand this phenomenon in the clinical setting, we studied a series of head-injured patients in whom multiple cranial computed tomographic (CT) scans were obtained. Patients whose follow-up CT studies revealed new intracranial lesions or worsening, compared with admission findings, were considered to have delayed cerebral injury. One hundred forty-nine (44.5%) of 337 consecutively studied patients developed delayed brain injury. There were highly significant associations (P < 0.001) between the appearance of delayed cerebral insults and the severity of the initial brain injury, the need for cardiopulmonary resuscitation in the field, the presence of coagulopathy at admission, and subdural hematoma on the initial CT scan. In addition, delayed injury was associated (P < 0.001) with higher mortality, slowed recovery, and poorer outcome at 6 months. Delayed brain injury was not significantly associated with patient age, sex, injury mechanism, associated injury, the need for endotracheal intubation in the field, early talking, CT abnormality other than intracranial hematoma, or type of residual neurological deficits. We used multiple regression analysis to explore the relationship between severity of injury, delayed insults, and outcome. As expected, the severity of the initial brain trauma contributed significantly to neurological outcome. The presence of delayed cerebral injury makes the outcome dramatically worse for each category of initial injury severity. The relationship between initial and secondary brain injury is discussed.

Adolescent↗