Retrograde perfusion sphincterometry with a flexible cystoscope: method of troubleshooting the AMS 800.

We developed the technique of retrograde perfusion sphincterometry to troubleshoot the AMS 800 device. We implanted artificial urinary sphincters in men who were incontinent after prostatectomy and performed intraoperative retrograde perfusion sphincterometry. Retrograde perfusion sphincterometry using a flexible cystoscope is simple and allows early recognition of intraoperative urethral injury and mechanical malfunction.

Mild hypothermia: an alternative to deep hypothermia for achieving neuroprotection.

The role of excitotoxins in the ischemic cascade that results in ischemic neuronal death has been clearly defined and has brought about attempts to halt the progression of neurologic damage. Improved understanding of this process has allowed for the development of interventions to optimize neurologic outcome following periods of ischemia. Deep hypothermia (15-22 degrees C) has long been recognized as one method of achieving neuroprotection, but is not without serious implications and risks to the patient. Mild hypothermia (32-34 degrees C) is evolving as an alternative neuroprotective measure that has been shown to improve neurologic outcome in experimental models of ischemia and head injury, as well as in recent head injury clinical trials. It has been safely used intraoperatively in a large series of patients undergoing craniotomy. Mild hypothermia is a technique that may soon be commonly employed alone or in conjunction with other methods of neuroprotection. Nurses caring for patients undergoing this technique must be aware of the practice implications associated with this procedure and adapt their care accordingly.

Dose escalation safety and tolerance study of the competitive NMDA antagonist selfotel (CGS 19755) in neurosurgery patients.

Selfotel (CGS 19755), a competitive N-methyl-D-aspartate antagonist, is neuroprotective in experimental models of ischemic cerebral injury. We studied the safety and tolerability of a single intravenous dose (0.5 to 2.0 mg/kg) of selfotel in neurosurgery patients. Thirty-two neurosurgical patients undergoing intracranial surgery were given ascending doses of selfotel 2 to 14 h before surgery. Serum selfotel levels were measured over a period of 24 h. Cerebrospinal fluid (CSF) levels were measured 1.5 to 18 h after dosing. Frequent side effects included psychomimetic symptoms such as hallucinations, abnormal dreaming, agitation, and paranoia among 20 (66%) patients. Ataxia was seen among five (16%) and dizziness among eight (25%). Symptoms occurred 38 min to 40 h from administration and persisted 5 min to 4 days. Symptom severity worsened with increasing area under the curve measurements and doses above 1.0 mg/kg. All symptoms were reversible and easily treated with intravenous haloperidol. Modest elevations of hepatic enzymes were observed among four patients. No patient had severe adverse reactions. Maximum selfotel levels attained were 143 mumol (serum) and 4.76 mumol (CSF). Peak serum levels among six patients were within potentially neuroprotective ranges. CSF levels remained detectable up to 18 h after dosing. No obvious relationship was seen between CSF drug levels and symptoms. Selfotel in doses of 0.5 to 2.0 mg/kg can be administered safely to neurosurgical patients. Maximum serum levels attained were within the range shown to be neuroprotective in experimental studies. Side effects even at the highest levels are tolerable and reversible. Selfotel use in patients at risk for cerebral injury should be further explored.

Dose escalation safety and tolerance study of the N-methyl-D-aspartate antagonist dextromethorphan in neurosurgery patients.

Experimental studies have shown that dextromethorphan, a noncompetitive N-methyl-D-aspartate antagonist is neuroprotective in experimental models of ischemic cerebral injury. The authors studied the safety and tolerability of oral dextromethorphan (DM) in humans, and correlated serum levels of this drug with cerebrospinal fluid (CSF) and brain levels. Neurosurgical patients undergoing intracranial surgery or endovascular procedures were given ascending doses of oral DM prior to and 24 hours after surgery. Serum, CSF, and brain levels of DM and its active metabolite, dextrorphan, were measured. One hundred eighty-one patients received a total of 212 courses of DM treatment in dose ranges of 0.8 to 9.64 mg/kg. Serum DM levels correlated highly with CSF and brain DM levels. Brain levels were 68-fold higher than serum levels, whereas CSF levels were fourfold lower than serum levels. The maximum DM levels attained were 1514 ng/ml (serum) 118 ng/ml (CSF), and 92,700 ng/g (brain). The maximum dextrorphan levels were 501 ng/ml (serum), 167 ng/ml (CSF), and 6840 ng/g (brain). In 11 patients, brain and plasma levels of DM were comparable to levels that have been shown to be neuroprotective in animal studies. Frequent side effects occurring at neuroprotective levels of DM included nystagmus (64%), nausea and vomiting (27%) distorted vision (27%), feeling "drunk" (27%), ataxia (27%), and dizziness (27%). All symptoms were reversible and no patient suffered severe adverse reactions. This study demonstrates that potentially neuroprotective doses of DM can be administered safely to neurosurgical patients. Brain and CSF levels of DM can be estimated from serum levels of the drug. Side effects, even at the highest levels, proved to be tolerable and reversible. Administration of DM to patients at risk for cerebral injury should be further explored.

Innovations in aneurysmal subarachnoid hemorrhage: intracisternal t-PA for the prevention of vasospasm.

Aneurysmal subarachnoid hemorrhage (SAH) affects approximately 30,000 people each year in North America. At least 30% of these patients will develop vasospasm as a result of the initial hemorrhage, and two thirds of these develop permanent disabilities or die. Blood deposited into the basal cisterns from the ruptured aneurysm can form thick clots around the major cerebral vessels. The by-products of the hemolyzed clots are believed to be responsible for the subsequent development of vasospasm. Hypervolemic, hypertensive, hemodilution therapy (HHHT) and nimodipine may improve outcome in some cases but there is no therapy known to prevent vasospasm in all patients. One potential therapeutic agent under investigation is tissue plasminogen activator (t-PA), a fibrinolytic enzyme. Instilled into the basal cisterns at time of aneurysm clipping, t-PA dissolves the clot so spasmogenic substances may be removed, thus preventing or reducing the severity of vasospasm.

MR and cerebrospinal fluid enzymes as sensitive indicators of subclinical cerebral injury after open-heart valve replacement surgery.

PURPOSE: To evaluate MR imaging and lumbar cerebrospinal fluid enzymes as potential sensitive indicators of cerebral injury after open-heart valve replacement surgery. METHODS: Thirty-four patients with cardiac valvular disease were prospectively entered into this study and then underwent valve replacement or repair under cardiopulmonary bypass using a membrane oxygenator. In 26 patients, MR head images were obtained 12 to 24 hours before surgery; repeat MR images were obtained between 1 and 2 weeks after surgery. In 18 patients, lumbar puncture cerebrospinal fluid was analyzed 24 to 48 hours after surgery; the analyses included measurement of lactic dehydrogenase, creatine phosphokinase, adenylate kinase, and neuron-specific enolase. RESULTS: After surgery, MR imaging showed new ischemic lesions in 15 (58%) of 26 patients: 7 with deep white matter hyperintense lesions; 5 with brain stem, caudate, cerebellar, or thalamic/basal ganglia infarcts; 1 with intraparenchymal hemorrhage; 1 with a subdural hematoma and cortical infarct; and 1 with a corpus callosum lesion consistent with calcium or air. These new ischemic lesions seen on MR images were associated with a focal neurologic deficit in only 4 (27%) of the 15 patients. Neuron-specific enolase and lactic dehydrogenase were abnormally elevated after surgery in 5 (28%) of 18 patients. Adenylate kinase and creatine phosphokinase (brain isozymes) were elevated in one (67%) of the patients. Two (40%) of the five patients with abnormally high neuron-specific enolase or lactic dehydrogenase after surgery also showed a new focal neurologic deficit. CONCLUSIONS: MR imaging is a sensitive measure of subclinical cerebral ischemia after cardiac valve replacement under cardiopulmonary bypass. Cerebrospinal fluid neuron-specific enolase and lactic dehydrogenase are less sensitive than MR imaging for detecting subclinical cerebral ischemia, but these values were elevated after surgery more frequently than was adenylate kinase in our patients.

Transcranial Doppler: correlation of blood velocity measurement with clinical status in subarachnoid hemorrhage.

Subarachnoid hemorrhage affects approximately 30,000 people each year in North America. Up to 50% of patients who survive the initial hemorrhage experience cerebral vasospasm, often resulting in permanent disability or death. Early detection allows interventions which may prevent catastrophic complications. Diagnosing vasospasm has always been dependent on invasive testing and correlation of the clinical picture. Alterations in neurological assessment, including Glasgow Coma Scale score changes, merely reflect poor cerebral perfusion secondary to the vasospasm, and may not be apparent for days. Transcranial Doppler (TCD) ultrasonography is an exciting diagnostic alternative. This noninvasive test may be done daily at the bedside, and may accurately predict impending vasospasm.

Salpingo-vesical fistula. Rare and unusual complication of vaginal hysterectomy.

A case of salpingo-vesical fistula is presented which occurred in a forty-six-year-old female two years after a vaginal hysterectomy. The patient's presenting complaints included pelvic and right lumbosacral discomfort, aggravated by urination. Cystoscopy revealed the fistula, and the patient was successfully treated with a salpingo-oophorectomy.

Molecular cloning and characterization of murine leukemia virus-related DNA sequences from C3H/HeN mouse DNA.

Ten murine leukemia virus (MuLV)-related DNA sequences were isolated from C3H/HeN mouse genomic DNA by cloning of EcoRI fragments in a Charon 4A vector. Detailed restriction endonuclease maps of four of the clones were developed by using AKR MuLV [32P]cDNA as a probe. C3H clone 14-9 contains approximately 7 kilobase pairs of MuLV-related DNA, one copy of an MuLV long terminal repeat-like sequence, and a region of flanking mouse DNA. C3H clones 34.2 and 36.1 contain approximately 2 kilobase pairs of MuLV-related DNA, one copy of a MuLV LTR-like sequence, and differing lengths of flanking mouse DNA sequences. C3H clone 8.13 was found to contain an insert of 5.7 kilobase pairs of MuLV-related DNA with two long terminal repeat-like regions and sequences which are partially homologous to AKv-1. Comparison fo the restriction endonuclease cleavage maps of these C3H clones with maps recently developed for ecotropic and xenotropic MuLV DNAs indicates that C3H clone 14-9 corresponds to the 5'-terminal portion of a genomic DNA sequence related to xenotropic MuLVs, whereas C3H clones 34.2 and 36.1 correspond to the 3' terminal portions of genomic DNA sequences related to xenotropic MuLVs. Clone 8.13 represents a deleted, xenotropic MuLV-related provirus. C3H clones 14-9, 34.2, 36.1, and 8.13 provide defined DNA sequence probes with which to characterize the organization and expression of endogenous MuLV-related DNA sequences in the mouse genome.

Immunological characterization of multiple weight forms of human cell plasminogen activators.

Several molecular weight forms of plasminogen activator (PA) activity have been observed in serum-free conditioned media from human cells in culture. An antibody inhibition technique is described which combines inhibition of enzyme activity by anti-urokinase IgG with sodium dodecyl sulfate-gel electrophoresis to determine whether different molecular weight forms of human cell PA's are immunologically related to urokinase. Plasminogen activator forms with molecular weights of 85,000 to 95,000, 50,000 to 60,000, and 36,000 were inhibited by anti-urokinase IgG. In contrast, PA forms with molecular weights in the 73,000 range from three different types of human cells were not inhibited by comparable concentrations of the antibody. Human embryonic kidney cultures contain only anti-urokinase IgG-inhibitable PA forms, while melanoma-derived Malme-3M cultures contain only anti-urokinase IgG-resistant forms. Cultures of tumorigenic Detroit 562 cells and nontumorigenic IMR-90 cells contain a mixture of "antibody-sensitive" and "antibody-resistant" PA forms. The antibody-resistant 73,000-dalton PA form may be a precursor of the smaller antibody-sensitive, urokinase-related forms, or it may be the product of a second plasminogen activator gene which codes for a protein immunologically and structurally different from urokinase.

Assessment of plasminogen synthesis in vitro by mouse tumor cells using a competition radioimmunoassay for mouse plasminogen.

A sensitive, specific competition radioimmunoassay for mouse plasmin(ogen) has been developed in order to determine whether mouse tumor cells can synthesize plasminogen in vitro. The rabbit anti-BALB/c mouse plasminogen antibodies used in the assay react with the plasminogen present in serum from BALB/c, C3H, AKR and C57BL/6 mice, and also recognized mouse plasmin. The competition radioimmunoassay can detect as little as 50 ng of mouse plasminogen. No competition was observed with preparations of fetal calf, human and rabbit plasminogens. A variety of virus-transformed and mouse tumor cell lines were all found to contain less than 100 ng mouse plasminogen/mg of cell extract protein. Thus, if the plasminogen activator/plasmin system is important in the growth or movement of this group of tumor cells, the cells will be dependent upon the circulatory system of the host for their plasminogen supply.

Fetal vesicoureteral reflux.

Intrauterine fetal vesicoureteral reflux has been demonstrated in a 25-week fetus. A voiding cystourethrogram when the patient was 1 year old showed persistence of the bilateral reflux. No urinary tract infectious have been documented. A survey of other physicians performing fetal transfusions indicates that fetal cystograms are infrequently obtained and that vesicoureteral reflux has been observed by ourselves and one other contributing physician. The incidence of reflux in fetal cystograms reviewed appears to be higher than would be expected when compared to normal premature babies, newborns, infants and children. This procedure provides an unusual opportunity to document intrauterine fetal vesicoureteral reflux and later obtain followup cystourethrograms in these children to determine the resolution or progression of this urinary tract abormality.