Analysis of steroid hormones and their conjugated forms in water and urine by on-line solid-phase extraction coupled to liquid chromatography tandem mass spectrometry.

BACKGROUND: In recent years, endocrine disrupting compounds (EDCs) have been found in rivers that receive significant inputs of wastewater. Among EDCs, natural and synthetic steroid hormones are recognized for their potential to mimic or interfere with normal hormonal functions (development, growth and reproduction), even at ultratrace levels (ng L(-1)). Although conjugated hormones are less active than free hormones, they can be cleaved and release the unconjugated estrogens through microbial processes before or during the treatment of wastewater. Due to the need to identify and quantify these compounds, a new fully automated method was developed for the simultaneous determination of the two forms of several steroid hormones (free and conjugated) in different water matrixes and in urine. RESULTS: The method is based on online solid phase extraction coupled with liquid chromatography and tandem mass spectrometry (SPE-LC-MS/MS). Several parameters were assessed in order to optimize the efficiency of the method, such as the type and flow rate of the mobile phase, the various SPE columns, chromatography as well as different sources and ionization modes for MS. The method demonstrated good linearity (R(2) > 0.993) and precision with a coefficient of variance of less than 10 %. The quantification limits vary from a minimum of 3-15 ng L(-1) for an injection volume of 1 and 5 mL, respectively, with the recovery values of the compounds varying from 72 to 117 %. CONCLUSION: The suggested method has been validated and successfully applied for the simultaneous analysis of several steroid hormones in different water matrixes and in urine.

Surgery for intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) represents 8 to 15% of all strokes in the United States and 20 to 30% of all strokes in Japan and China. Although ICH represents a relatively small fraction of total strokes, it is a formidable disease, with a 30-day mortality rate two- to sixfold higher than that for ischemic stroke. Furthermore, it is a major cause of disability, with only 20% of patients becoming independent at 6 months. The most common risk factors for ICH are age, hypertension, and amyloid angiopathy, which are associated with damage to and weakening of the arterial/arteriolar wall leading to vessel rupture. The pathology is a dynamic one that continues to evolve over the first few days after onset. In 20 to 30% of ICH, clot volume increases over the first 24 hours and is generally associated with neurologic worsening. The final outcome from ICH is related not only to clot volume, compression, and destruction but also to potential neurotoxicity from the blood degradation products and associated neuronal ischemia. The treatment of ICH has been one of the most controversial and least well-studied areas from a medical or surgical perspective. Surgical treatment has evolved over the years and can be grouped into open and stereotactically guided surgery for hematoma evacuation. Seven thousand operations per year are performed in the United States for hematoma evacuation, although this approach has not been adequately investigated. Adjuvant medical therapies with neuroprotective agents require further investigation and may potentially have additive benefits.

Legionella myositis.

Neuromuscular involvement in patients with legionnaires' disease is common, with serum CK elevations in up to 78% of patients. A few cases have been associated with neuropathy. The mechanism of injury to the neuromuscular system is unknown, but organisms have not previously been found in nerve or muscle. We report the clinical, electrophysiologic, and pathologic findings in a patient with Legionella myositis and motor neuropathy, the first case to demonstrate direct muscle invasion by the Legionella organism.

Pulmonary arteriovenous malformations: cerebral ischemia and neurologic manifestations.

BACKGROUND: There is an increasingly recognized association between pulmonary arteriovenous malformations (PAVM) and cerebral ischemia, frequently attributed to paradoxical embolization. PAVM occur in 20 to 30% of the hereditary hemorrhagic telangiectasia (HHT) population. OBJECTIVE: To evaluate the risk determinants for cerebral ischemia and neurologic manifestations in patients with PAVM. METHODS: A retrospective cross-sectional study was performed on consecutive patients admitted between 1988 and 1992 for treatment of PAVM. The number of PAVM, feeding artery (FA) diameters, and aneurysmal sizes were determined by pulmonary angiography. Patients were categorized as having single or multiple PAVM with an FA diameter of > or = 3 mm. History, examination, and cerebral imaging studies were used to determine the prevalence of neurologic manifestations. Patients were defined as having cerebral paradoxical embolization if there was radiologic evidence of cortical infarction. RESULTS: There were 75 cases: 26 single PAVM and 49 multiple PAVM. Cortical infarction was present in 14% of patients with single PAVM. Patients with multiple PAVM had a greater prevalence of any infarction (OR 3.2; 95% CI, 1.2 to 9.44, p = 0.030), cortical infarctions (OR 2.3; 95% CI, 0.58 to 9.2, p = 0.230), subcortical infarctions (OR 2.1; 95% CI, 0.58 to 7.95, p = 0.249), abscesses (OR 2.3; 95% CI, 0.46 to 11.94; p = 0.295), and seizures (OR 6.4, 95% CI 0.77 to 53.2, p = 0.054). Patients with multiple PAVM had markedly greater odds of having any clinical or radiologic evidence of cerebral ischemic involvement (OR 4.5; 95% CI, 1.47 to 14; p = 0.008). CONCLUSION: There is a strong association between single PAVM and various neurologic manifestations. The prevalence is greater for patients with multiple PAVM, suggesting increased predisposition for paradoxical embolization with a greater number of malformations.

Spectroscopic imaging of stroke in humans: histopathology correlates of spectral changes.

Previous studies of human stroke by 1H nuclear magnetic resonance spectroscopy have shown elevation of lactate lasting 3 to 6 months. Complete metabolic turnover of the elevated lactate pool has been demonstrated 5 weeks after a stroke. Its cellular localization is among the first questions requiring clarification. Information pertinent to this question came to us from a patient with a 2-week-old stroke by 1H nuclear magnetic resonance spectroscopic imaging 1 week before his death led to neuropathologic examination of the brain. 1H spectra from voxels including the infarcts showed increased lactate and decreased N-acetylaspartate. Histopathology showed sheets of foamy macrophages in the infarct, but few neurons. Macrophage density ranged from 196 cells/mm2 near the surface of the infarct to 788 near its medial margin. Glial density was 500 to 800 cells/mm2. Lactate concentration in voxels including portions of the infarct was estimated at 7 to 14 mM. Voxels showing low N-acetylaspartate and high lactate on spectroscopic imaging were associated with histopathologic sections containing foamy macrophages. Brain macrophages--which begin to appear 3 days after infarction and gradually disappear over several months--could be a major source of elevated lactate signals that persist for months after stroke.

A comparative study of the cerebrovascular complications of cocaine: alkaloidal versus hydrochloride--a review.

Cocaine, especially in its alkaloidal or "crack" form, has been increasingly associated with cerebrovascular disease. Before the crack epidemic, cocaine hydrochloride (HCl) was also implicated as a cause of stroke. However, less is known about the differences in stroke subtypes, age at stroke onset, or presence of underlying structural cerebrovascular disease with different forms of cocaine use. We compared 26 patients (previously reported) from our four institutions plus 16 cases reported in the literature of stroke associated with alkaloidal cocaine to 63 (57 reported in the literature and six not previously reported from our four institutions) cases of stroke associated with cocaine HCl. Ischemic and hemorrhagic strokes are equally likely after alkaloidal cocaine use, whereas cocaine HCl is more likely (approximately 80% of the time) to cause hemorrhagic stroke, with approximately half the intracranial hemorrhages occurring from ruptured cerebral saccular aneurysms or vascular malformations. The presence of an underlying cerebral aneurysm was more common among patients with cocaine HCl-associated strokes than alkaloidal cocaine-associated strokes. Cerebral infarction was significantly more common among the alkaloidal cocaine users than in all the cocaine HCl users, and this was also true when alkaloidal cocaine users were compared with parenteral cocaine HCl (intravenous and intramuscular) users. Only hemorrhagic stroke has been reported with intravenous cocaine HCl use. We conclude that the pathogenesis of cocaine-related stroke is heterogeneous, and depends, in part, on the form of cocaine used.

Embolotherapy of large pulmonary arteriovenous malformations: long-term results.

BACKGROUND: The purpose of this study was to document the long-term results of transcatheter embolotherapy of large pulmonary arteriovenous malformations (PAVMs). METHODS: From a data base of 221 consecutive patients with PAVMs treated by embolotherapy between 1978 and 1995, 45 patients with 52 PAVMs, supplied by feeding arteries 8 mm in diameter or larger, were selected for a retrospective investigation. RESULTS: Of 45 patients with 52 large PAVMs, 38 patients (84%) with 44 PAVMs (85%) were cured by the first embolotherapy (mean follow-up, 4.7 years). Acute periprocedural complications included self-limited pleurisy (31%), angina secondary to air embolus (2%), and paradoxical embolization of a device during deployment (4%). None of these events led to short- or long-term sequelae. Seven patients (16%) had persistence of the PAVM attributable to either recanalization (n = 4) or interim accessory artery growth (n = 3). Two of these patients presented with ischemic stroke several years after the initial treatment. Persistent PAVMs (n = 8) were retreated successfully by a second procedure (n = 7), or a third procedure (n = 1) (mean follow-up, 5.9 and 5.3 years, respectively). CONCLUSIONS: Embolotherapy of large PAVMs results in permanent occlusion in an overwhelming majority of patients. Continued patency due to recanalization or accessory artery growth is easily detected and treated.

Middle cerebral artery blood velocity during controlled ovarian hyperstimulation.

OBJECTIVE: To measure cerebral blood flow velocities using transcranial Doppler during ovulation induction after pituitary suppression. DESIGN: Women undergoing controlled ovarian hyperstimulation after pituitary suppression were prospectively studied. SETTING: Tertiary institution. PATIENTS: A microprocessor-controlled directional pulsed-wave adjustable hand held probe (2 MHz) was used to measure blood flow velocities and pulsatility indices in the right and left middle cerebral arteries (middle cerebral artery) in nine patients. Measurements of peak middle cerebral artery velocities (cm/s) and pulsatility index were obtained after achieving pituitary suppression with leuprolide acetate and repeated over several days after treatment with human menopausal gonadotropin (225 IU/d). RESULTS: There was a significant increase in the peak middle cerebral artery velocities (cm/s) of the patients measured at the time of pituitary suppression when compared with those obtained at the time of maximal estradiol (E2) (98 +/- 12 versus 105 +/- 12, P less than 0.03). The pulsatility index also showed a significant increase from 0.72 +/- 0.08 at the time of pituitary suppression to 0.82 +/- 0.04 at the time of maximal hyperestrogenism, P less than 0.002. Estradiol values obtained at the time of the transcranial Doppler examinations were normalized by transformation to their natural logarithms (LnE2). The middle cerebral artery velocities were significantly correlated with LnE2 levels (P less than 0.0001 and r = 0.93). CONCLUSION: Estrogen levels appear to be directly correlated with cerebral blood flow velocity and pulsatility index, implying an effect of ovarian steroids on cerebrovascular hemodynamics.

Exceptional multiplicity of cerebral arteriovenous malformations associated with hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome).

PURPOSE: To describe the clinical and imaging features of seven patients with hereditary hemorrhagic telangiectasia and an exceptional number of cerebral arteriovenous malformations (AVMs). METHODS: One hundred thirty-six patients from a dedicated hereditary hemorrhagic telangiectasia clinic were screened systematically for cerebral AVMs by means of MR imaging. Thirty-one were found to have abnormalities suggestive of a vascular malformation. Eighteen of these 31 patients subsequently underwent diagnostic cerebral angiography. RESULTS: Of the 18 patients who had cerebral angiography, all were found to have at least one AVM and seven were found to have three or more AVMs. The number of cerebral AVMs detected ranged from three to nine. At angiography, the AVMs varied in size from 3 to 25 mm in maximal dimension and consisted of a poorly defined plexiform nidus that typically had a single arterial feeding pedicle and a single draining vein. The two largest AVMs (20- and 25-mm nidus, respectively) contained intranidal aneurysms. Treatment included embolization, surgical excision, or follow-up management. CONCLUSIONS: Multiple cerebral AVMs are associated with hereditary hemorrhagic telangiectasia and further highlight the uniqueness of central nervous system involvement by this systemic angiodysplasia. MR imaging can underestimate the number and size of cerebral AVMs; therefore, catheter angiography is necessary to establish the extent of central nervous system involvement in this disorder.

MR of hereditary hemorrhagic telangiectasia: prevalence and spectrum of cerebrovascular malformations.

PURPOSE: Our goal was to describe the prevalence and types of cerebral vascular malformations (CVMs) seen with MR imaging in patients with hereditary hemorrhagic telangiectasia (HHT). METHODS: We reviewed retrospectively the brain MR images of 184 consecutive patients with HHT. Catheter angiography was performed in 17 patients with CVMs detected on MR images. RESULTS: MR imaging revealed 63 CVMs in 42 patients. Classic arteriovenous malformations (n = 10) had a conspicuous network of vessels with flow voids and enlarged adjacent pial vessels. Apparent venous malformations (n = 5) were best seen after administration of contrast material as a prominent vessel coursing through normal brain parenchyma. Indeterminate vascular malformations (n = 48) had a spectrum of appearances characterized by variable combinations of heterogeneous signal intensity, enhancement, or hemosiderin. Angiography in 17 patients revealed 47 CVMs. Forty-six were arteriovenous malformations (AVMs), including 25 CVMs not seen with MR imaging and 21 CVMs that by MR criteria included 8 AVMs and 13 indeterminate vascular malformations. Angiography confirmed 1 venous malformation seen with MR imaging but failed to detect 3 indeterminate lesions revealed by MR imaging. CONCLUSION: MR imaging of a large cohort of consecutive patients with HHT revealed a CVM prevalence of 23% (42/184). Most CVMs (48/63) have an atypical appearance for vascular malformations on MR images. Angiographic correlation suggests that MR imaging underestimates the prevalence of CVMs and that the majority of indeterminate CVMs, despite their variable MR appearance, are AVMs.

Painless aortic dissection presenting as a progressive myelopathy.

We report a patient with a painless aortic dissection whose neurologic symptoms progressed over 5 days to a complete transverse myelopathy. She did not experience pain as her neurologic deficits evolved. Magnetic resonance imaging revealed a thoracic aortic dissection extending from the arch to the level of the 12th thoracic vertebra and demonstrated ischemic changes in the spinal cord and one thoracic vertebral body. Aortic dissection must be included in the differential diagnosis of spinal cord syndromes even in the absence of pain. Early recognition of aortic dissection as a cause of progressive myelopathy may become increasingly important as new therapies for central nervous system ischemia are developed.

Occipital lobe vascular malformations: prevalence of visual field deficits and prognosis after therapeutic intervention.

BACKGROUND: The prevalence of visual field (VF) deficits in association with vascular malformations of the occipital lobe is not known, and the prognosis of the VF after therapeutic intervention has not been systematically documented. METHODS: We reviewed the clinical records of 23 consecutive patients who were managed at a single institution during a 3-year period with intracranial vascular malformations extending within the anatomic borders of the occipital lobe. Lesion location and treatment rendered were correlated with formal VF testing performed before and after therapeutic intervention. RESULTS: Twenty-one of the 23 patients underwent treatment of their lesions. Treatment included resection after preoperative embolization (12 patients), resection alone (2 patients with arteriovenous malformations and 3 patients with cavernous malformations), and stereotactic radiosurgery (4 patients; preceded by embolization in 3 of the 4). One patient was followed expectantly, and another died as a result of hemorrhage soon after undergoing endovascular embolization. The VFs were assessed before and after therapeutic intervention (follow-up assessment, 2-29 mo). New VF deficits or worsening of preexisting VF deficits were documented in 5 of the 21 treated patients (24%), but only 2 of these patients (9.5%) had persistent deficits at the time of their follow-up examinations. Among the 10 patients with pretreatment VF deficits, 5 improved and the other 5 were unchanged after treatment. CONCLUSION: Patients with occipital lobe vascular malformations frequently present with associated VF deficits. Surgical resection or stereotactic radiosurgery (with or without previous embolization) of these lesions can be performed with little risk of causing new VF deficits or worsening of preexisting ones. Many VF deficits can be expected to improve or resolve after therapy.

Single-photon emission computed tomography in distal field hypoperfusion.

To assess the ability of technetium-99m hexamethylpropyleneamineoxime single-photon emission computed tomography (SPECT) imaging to differentiate distal field hypoperfusion from other stroke mechanisms, 24 patients with acute cerebral ischemia were studied. SPECT scans were read by two physicians according to a preestablished set of criteria for distal field hypoperfusion. SPECT patterns read as "probable" or "definite" for distal field hypoperfusion were found in 42% (10/24); of these, 80% (8/10) had ipsilateral carotid occlusion or high-grade stenosis. Severe carotid stenosis was found in 43% (6/14) with SPECT scans negative for distal field hypoperfusion (Fisher exact test [1-tailed] p = 0.0796). The results suggest that a distal field hypoperfusion pattern on SPECT may identify patients with hemodynamically significant large vessel disease.

Transcranial Doppler validation pilot study.

The use of transcranial Doppler sonography (TCD) for the evaluation of patients with ischemic cerebrovascular disease remains controversial. This study was organized to gather preliminary data regarding the sensitivity and specificity of TCD when compared to cerebral angiography in detecting stenosing lesions and collateral flow patterns of the anterior cerebral circulation. Forty-two patients from six medical centers were prospectively enrolled. Each received cerebral angiography and TCD testing within 24 hours of each other. Based on TCD criteria established a priori, the results were first analyzed by a blinded investigator and then by computer. Computerized analyses were then repeated with modified criteria. Collateral flow through the anterior communicating and ophthalmic arteries was detected with sensitivities of 62% and 100%, and specificities of 98% and 92%, respectively. Internal carotid artery proximal and distal severe ( greater than 70%) stenoses were detected with sensitivities of 79% and 100% and specificities of 88% and 97%. Middle and anterior cerebral artery stenoses and middle cerebral artery occlusion were detected with specificities exceeding 98%; however, the data were insufficient to determine sensitivity. Computerized analyses did not permit improvement of sensitivity and specificity of the baseline criteria. The selected TCD criteria are highly specific in detecting intracranial stenoses and collateral flow patterns of the anterior circulation. The criteria have limited but acceptable sensitivity and specificity in detecting internal carotid artery origin severe stenoses, and are highly sensitive in detecting ophthalmic artery retrograde flow. A study with a larger sample is necessary to provide definitive guidelines for diagnosis.

Clivus and cervical spinal osteomyelitis with epidural abscess presenting with multiple cranial neuropathies.

A 65-year-old diabetic man with a history of otitis was admitted with headache, neck and shoulder pain and cranial nerve abnormalities including sixth, seventh and twelfth nerve palsies, hearing loss and ptosis. Lumbar puncture revealed an elevated CSF protein and pleocytosis. Imaging procedures demonstrated osteomyelitis of the clivus that involved the epidural space and extended within the prevertebral space to the cervical spine. The patient improved after treatment with antibiotics and immobilization of the neck. This case illustrates the importance of recognizing infections of the clivus in patients with cranial nerve abnormalities.

Failure of the hypotensive provocative test during temporary balloon test occlusion of the internal carotid artery to predict delayed hemodynamic ischemia after therapeutic carotid occlusion.

BACKGROUND: Extensive experience and critical evaluation of the efficacy of a pharmacologic hypotensive challenge during conventional balloon test occlusion (BTO) of the internal carotid artery (ICA) is lacking. This prompted us to review our institution's most recent experience with this adjunctive provocative test before planned therapeutic balloon occlusion of the ICA. METHODS: Twenty consecutive cases of endovascular therapeutic balloon occlusion of the ICA were retrospectively reviewed. Conventional BTO under normotension and with hypotensive challenge were performed within a standardized protocol. RESULTS: Sixteen patients underwent provocative testing, of which 13 had BTO with hypotensive challenge. All patients in this group tolerated these maneuvers without acute neurologic deficit. Two (15%) of these patients developed delayed permanent neurologic deficits, which seemed to be attributable to hemodynamic ischemia. One of seven patients not undergoing hypotensive challenge also developed transient neurologic deficits after carotid occlusion. CONCLUSIONS: Despite the conceptually attractive and early positive experience of the hypotensive challenge in attempting to increase sensitivity and specificity of risk for developing delayed hemodynamic ischemia, we have found two significant false-negative results. This experience is reviewed in the context of risks of permanent balloon occlusion of the carotid artery after balloon test occlusion.

Transient ischemic attacks in the elderly: diagnosis and treatment.

Transient ischemic attacks (TIAs) are the most reliable warning sign of impending stroke and are highly indicative of significant coronary artery disease. The history and physical examination may suggest the pathologic mechanism, an important clue to diagnosis and prognosis. Diagnostic testing is individualized but often includes ECG and cerebral contrast angiography. Exercise testing, echocardiography, ultrasound, CT, and/or MRI are sometimes indicated. The patient with recent TIAs may be hospitalized for acute management. Long-term treatment includes stroke risk factor modification, use of antiplatelet agents, and sometimes anticoagulant therapy. Selected older patients may be candidates for carotid endarterectomy.

Protocols and critical pathways for stroke care.

We have presented a conceptual approach toward developing clinical protocols and critical pathways in a complex multidisciplinary environment with a commitment to clinical excellence, evidence-based practice methodology, and education. The process and the mood surrounding these have been more important in our view than any particular protocol or pathway. They have generated an attitude aiming toward avoidance of complications rather than crisis management. They have contributed to a philosophy of integrative multidisciplinary collaborations among various specialists, house staff, and nursing and paramedical personnel and a greater mutual sensitivity in interactions with medical center management and administration. The overall impact of this global approach has been quantifiable (Fig. 6), although the role(s) of one or more facets of it cannot be independently defined (21, 22). Protocols and clinical pathways should be viewed as components of total quality management. They should not be allowed to restrict the patient's or physician's choice of interventions, they should not inhibit in any way innovation or the introduction of novel methodologies. Yet, protocols and critical pathways should and do generate a pressure on every member of the health-care team, a sense of negative entropy constantly urging a move toward a higher level of excellence and quality.

Using a novel sol-gel stir bar sorptive extraction method for the analysis of steroid hormones in water by laser diode thermal desorption/atmospheric chemical ionization tandem mass spectrometry.

A new coating material was used for a stir bar sorptive extraction (SBSE) method coupled to a high throughput sample analysis technique. This allowed for a simple procedure for fast determinations of eight steroid hormones (estriol, estradiol, ethynylestradiol, estrone, progesterone, medroxyprogesterone, levonorgestrel, northindrone) in water. Sample pre-treatment was performed using an in-house SBSE method based on a polydimethylsiloxane/phenyltrimethylsiloxane/ß-cyclodextrin sol-gel material. The analytes were desorbed by liquid extraction prior to their analysis by laser diode thermal desorption/atmospheric pressure chemical ionization coupled to tandem mass spectrometry (LDTD-APCI-MS/MS). Several parameters, including ionic strength, volume and time of extraction as well as volume and time of desorption, were investigated to maximize extraction efficiency by SBSE in aqueous solutions. The in-house stir bar showed good reproducibility and could be used for at least 50 extractions without affecting analytical performance. The recoveries of the spiked steroid hormones ranged from 55% to 96% in all water matrices studied (HPLC grade water, tap water and raw wastewater). Only one compound showed poor recovery values (<2% for estriol) in all matrices. The method detection limits (MDLs) in real matrices were within the range of 0.1-0.3 µg L(-1) except for estriol at 48 µg L(-1). The extraction performance of the in-house SBSE for the eight selected hormones was also compared with that of a commercially-available stir bar coated with polydimethylsiloxane (PDMS). This novel stir bar coating could prove to be useful method for the detection and quantification of trace levels of steroid hormones.