Enalapril prevents imminent and reduces manifest cerebral edema in stroke-prone hypertensive rats

BACKGROUND AND PURPOSE: Stroke-prone spontaneously hypertensive rats (SHRSP), subjected to high NaCl intake, show severe hypertension, organ damage, and early death. Preventive treatment with an angiotensin-converting enzyme (ACE) inhibitor is known to reduce mortality. Previously we found that proteinuria always precedes cerebral edema in SHRSP. Hence, in this study ACE inhibition was started later, ie, directly after manifestation of either proteinuria or cerebral edema. METHODS: SHRSP were subjected to 1% NaCl intake. Group 1 served as a control. In group 2 early-onset treatment with the ACE inhibitor enalapril was initiated after proteinuria was >40 mg/d. In group 3 late-onset ACE inhibition was started after the first observation of cerebral edema with T2-weighted MRI. Cerebral edema was expressed as the percentage of pixels with an intensity above a defined threshold. RESULTS: In controls median survival was 54 days (range, 32 to 80 days) after start of salt loading. The terminal level of cerebral edema was 19.0+/-3.0%. Under early-onset enalapril, median survival increased to 320 days (range, 134 to 368 days; P<0.01 versus group 1). Cerebral edema was prevented in all but 1 rat. Systolic blood pressure was slightly and transiently reduced at day 14. Proteinuria was markedly reduced (52+/-7 versus 190+/-46 mg/d in group 1 at day 7; P<0.05). Under late-onset enalapril, median survival was 264 days (range, 154 to 319 days; P<0.01 versus group 1). Cerebral edema decreased to baseline levels (9.6+/-2.9 at day 0 to 3.4+/-0.5% at day 3; (P<0.05). Ultimately cerebral edema reoccurred in 6 of the 8 rats. SBP decreased slightly at day 7 only. Proteinuria decreased from 283+/-27 at day 0 to 116+/-22 mg/d at day 7 (P<0.05). Complete remission of the original locus of cerebral edema was confirmed histologically. CONCLUSIONS: In SHRSP with proteinuria, treatment with an ACE inhibitor both prevented the development of cerebral edema and reduced manifest cerebral edema and proteinuria. Survival was markedly prolonged. These findings support the use of ACE inhibition for treatment in hypertensive encephalopathy.     

Sodium withdrawal contractures in developing and regenerating rat extensor digitorum longus muscles

During postnatal development of extensor digitorum longus (EDL) muscle, sodium withdrawal contractures were observed during the first 6 days after birth, and not after this time. In regenerating EDL muscles, zero-Na contractures were demonstrated: (1) 7 days after bupivacaine injection, but not 14 or 90 days after this injection; (2) 7, 14, and 90 days after autotransplantation; and (3) 7, 14, and 90 days after the intervention in sliced muscles. The present findings emphasize the role of the denervation in the development of zero-Na contractures in the regenerating muscles and suggest that a calcium-sodium exchange across the sarcolemma may appear in these muscles.     

Severe myogenic pain in an unfit subject after intensive and prolonged abdominal muscle exercise

The authors report the case of an unfit patient who, following intensive and prolonged physical exercise involving the abdominal muscles, presented a massive and diffuse subcutaneous edema (abdomen, scrotum, chest and face) together with abdominal and thoracic pain which increased in response to finger pressure. In addition, this was accompanied by a marked increase in CK, CK-MB and LDH, and TGO and TGP. Chest or heart pathologies were excluded by monitoring ECG and other clinical parameters, like heart rate and blood pressure, and by performing a chest X-ray. Muscular ultrasonography confirmed the massive subcutaneous edema and abdominal MR showed a slight edema in the suprasacral region, as well as confirming the subcutaneous edema. Hematological data gradually reduced and returned to normal after a week. Edema and pain also regressed gradually: the former finally disappeared after one week and the latter after five days. The authors conclude that clinical and laboratory findings were particularly severe because the subject was unfit and subcutaneous edema was larger than the free liquid in the abdominal cavity because the latter was absorbed by the peritoneum which acted as a dialysing membrane.     

Metalloproteinase inhibition blocks edema in intracerebral hemorrhage in the rat

Clinical worsening often occurs 1 to 2 days after an intracerebral hemorrhage. Extracellular matrix proteolysis by metalloproteinases, which attack the basal lamina and open the blood-brain barrier, may be one contributing factor. Matrix metalloproteinases and plasminogen activators are increased 16 to 24 hours after a bacterial collagenase-induced intracerebral hemorrhage, suggesting that agents that block metalloproteinases may reduce the brain swelling after hemorrhage. Therefore, we injected 0.2, 0.3, 0.4, or 0.5 units bacterial collagenase intracerebrally in rats to produce an intracerebral hemorrhage. Twenty-four hours later, brain tissue was removed for measurement of brain water and electrolytes. Proteases were assayed by zymography. Treatment with a matrix metalloproteinase inhibitor, BB-1101, was begun 6 hours after the collagenase lesion, when the hematomas were formed and the secondary edema was increasing. Bacterial collagenase caused a dose-dependent hematoma at the injection site with secondary brain edema in both posterior regions. The lower bacterial collagenase doses (0.2 and 0.3 units) mainly caused brain edema in the tissue around the injection site, whereas the higher doses (0.4 and 0.5 units) also affected the opposite hemisphere. Administration of BB-1101 significantly reduced the brain water and sodium contents in regions away from the injection site in rats with 0.4 unit lesions (p < 0.05). Zymography showed an increase in 92-kDa type IV collagenase and urokinase-type plasminogen activator at 24 hours. Inhibitors of proteolytic cascade enzymes may be useful in treatment of secondary brain edema in intracerebral hemorrhage.     

Effect of a local nonsteroidal anti-inflammatory drug on postoperative irritation after squint surgeries. Prospective randomized double-blind study

BACKGROUND: Topical application of a nonsteroidal antiphlogistic drug (NSAD) is often recommended to minimize postoperative lid and conjunctival edema. However, the effectiveness of such therapy remains controversial. PATIENTS AND METHODS: The study presented included 100 patients aged 23.6 +/- 19.5 (5 to 77) years, who were randomly assigned to two treatment groups. Group 1 included 50 patients who underwent squint surgery, and who received Flurbiprofen ED twice a day from the first preoperative day to the third postoperative day. Group 2 served as a control group. These patients were treated with the same regimen using artificial tears. The extent of lid and conjunctival edema was assessed and scored from 1 to 4 on the fourth postoperative day. RESULTS: Squint surgery was performed on 129 eyes of 100 patients. In 32 eyes (24.8%) one muscle was operated on. In 79 eyes (61.2%) 2 muscles and in 18 eyes (14%) three muscles were operated on. The average postoperative conjunctival edema score was 2.08 +/- 0.62 (Flurbiprofen group) and 2.04 +/- 0.67 (control group), respectively. The scoring values for lid edema were 1.90 +/- 0.54 and 1.82 +/- 0.43. The differences between the two groups were not statistically significant (P = 0.21 and 0.39; Mann-Whitney test). No influence of the patient's age on the development of lid and conjunctival edema could be detected (P > 0.08). However, the number of muscles that were operated on had a significant influence on both parameters (P = 0.01 and 0.028). Single muscle operations revealed the lowest scaling values (P < 0.02 and P < 0.04). No difference was found whether 2 or 3 muscles were operated on (P = 0.24 and 0.12). CONCLUSIONS: No beneficial effect of topical application of NSAD on postoperative lid and conjunctival edema could be found in this controlled study.     

Variations of the frontal exit of the supraorbital nerve: an anatomic study

Meningeal worm (Parelaphostrongylus tenuis) is a neurotropic nematode of ungulates in eastern North America. Lack of an effective diagnostic test increases the concern of translocating potentially infected ungulates into western North America, where P. tenuis does not occur naturally. In an attempt to identify serodiagnostic molecules, we determined (1) whether elk (Cervus elaphus) experimentally infected with P. tenuis produce antibodies against infective larvae or adult worms, and (2) if sera consistently recognize antigens that distinguish P. tenuis from a common nematode parasite of elk, the lungworm Dictyocaulus viviparus. Each of 10 elk were exposed to 15 or 300 infective P. tenuis larvae. Serum was collected (0, 41, and 83 days post-exposure and at necropsy) and monitored for antibodies using the enzyme-linked immunosorbent assay (ELISA) and immunoblot. When reactivity of sera with larval P. tenuis protein was compared (day 0 versus 83), ELISA values were significantly higher on day 83 for elk exposed to 15 or 300 parasites. Likewise, ELISA values using protein of adult P. tenuis were higher for elk exposed to 300 larvae. Immunoblots showed that sera from elk, with adult worms in the central nervous system, consistently recognized the 25-27, 28-30, and 34-36 kDa antigens of infective larvae after 83 days. However, many D. viviparus molecules were found to cross-react with antibodies formed against meningeal worm antigens. Use of adult worm proteins for serodiagnosis appears limited, because no protein was consistently recognized by sera collected from elk exposed to 15 larvae. We believe that development of a reliable diagnostic test for meningeal worm requires more research addressing cross-reactivity and detection of P. tenuis during the incubation stage.     

Interactions of polyclonal and monoclonal anti-glycoprotein 120 antibodies with oligomeric glycoprotein 120-glycoprotein 41 complexes of a primary HIV type 1 isolate: relationship to neutralization

The arterial ketone body ratio (AKBR) is considered to be an accurate index of the functional reserve of the liver, and the validity of this idea has been confirmed in the field of abdominal surgery. We found low AKBR value intracerebral hemorrhage patients and discussed the clinical significance of this finding in this paper. Twenty-five patients with intracerebral hemorrhage treated at our institution were included in this study. Their ages ranged from 42 to 86 years old (average 68.5 years). There were 13 cases of putaminal hemorrhage and 12 cases of thalamic hemorrhage. Evacuation of the hematoma or ventricle drainage was performed in 20 of these cases within 3 days after symptoms of intracerebral hemorrhage appeared. There were 12 cases with intraventricular hemorrhage. The outcome of these patients was as follows; 17 cases survived, eight cases died. We collected blood samples on days 1, 2, 3, 7 and 10 after the onset of symptoms (day 0) and measured the following: 1, beta-hydroxybutyrate; 2, acetoacetate; 3, epinephrine; 4, norepinephrine. On day 0 total ketone body levels were higher (246.3 +/- 231.7 mumol/l), AKBR values (0.60 +/- 0.18) were significantly lower than in the control group (2.05 +/- 1.35) (p < 0.001). However, both epinephrine and norepinephrine levels were significantly higher, 638.4 +/- 229.0 pg/ml and 1036.5 +/- 288.2 pg/ml, respectively. The AKBR value was 0.76 +/- 0.19 on day 1, 1.04 +/- 0.30 on day 2, and increased thereafter. In addition, the relation between sequential changes of AKBR in patients with intraventricular hemorrhage and outcome were also discussed. AKBR values are known to decrease not only in cases of hepatic failure, but in cases in which the liver energy charge is reduced, such as shock and hypoxemia, but no investigations have ever been performed to determine whether AKBR is altered in cerebrovascular disease. In this study, we found that AKBR values were lower in intracerebral hemorrhage, presumably due to reduced hepatic blood flow causes by increased levels of epinephrine and norepinephrine. In addition, our findings suggest that the fluctuations in AKBR values correlated with the outcome of intracerebral hemorrhage patients.     

The neuropathology of orthotopic liver transplantation: an autopsy series of 16 patients

OBJECTIVE: To examine the neuropathologic findings seen in the setting of orthotopic liver transplantation (OLT) and to asses the role, if any, that the neuropathology had in the patient's death. DESIGN: Retrospective autopsy series of 16 patients. SETTING: Tertiary referral center with a high volume of liver transplantation. PATIENTS: Sixteen OLT patients who died and in whom a complete autopsy, including examination of the brain and spinal cord, was performed. RESULTS: Sixteen patients, including 13 women and 3 men, comprised the study group. Patients ranged in age from 25 to 64 years (mean 44.8 years). Postoperative OLT survival ranged from 1 to 1962 days (mean 236 days). Reasons for the initial OLT included hepatitis (n = 6), fulminant hepatic failure (n = 4), cryptogenic cirrhosis (n = 2), methotrexate toxicity (n = 1), postoperative complication (n = 1), primary biliary cirrhosis (n = 1), and hepatocellular carcinoma (n = 1). Autopsies in 13 (81%) patients showed neuropathology; in only 2 patients, however, was the primary cause of death attributable to these findings. The most common neuropathology was related to anoxia or infarction, specifically, ischemia or focal neuronal necrosis (n = 9), infarction (n = 4), and diffuse anoxic encephalopathy (n = 3). Other central nervous system findings included infection with Aspergillus, Candida, and Toxoplasma (n = 3). The most common cause of death was infection-related in 8 patients. One patient died of pulmonary hypertension, 1 of acute rejection, and 1 of possible hyperacute rejection. Two patients died directly as a consequence of neuropathology findings; one had massive central edema with herniation, and the other had a large intracerebral hemorrhage with herniation. The exact cause of death was unclear in 3 patients. CONCLUSIONS: The most common neuropathology findings in this series were related to ischemia and infarction. Neuropathology findings are a significant cause of morbidity, but were only rarely the main cause of death (n = 2) in the OLT patients in this study.     

Matrix metalloproteinases and TIMPs are associated with blood-brain barrier opening after reperfusion in rat brain

BACKGROUND and PURPOSE: Reperfusion disrupts cerebral capillaries, causing cerebral edema and hemorrhage. Middle cerebral artery occlusion (MCAO) induces the matrix-degrading metalloproteinases, but their role in capillary injury after reperfusion is unknown. Matrix metalloproteinases (MMPs) and tissue inhibitors to metalloproteinases (TIMPs) modulate capillary permeability. Therefore, we measured blood-brain barrier (BBB) permeability, brain water and electrolytes, MMPs, and TIMPs at multiple times after reperfusion. METHODS: Adult rats underwent MCAO for 2 hours by the suture method. Brain uptake of 14C-sucrose was measured from 3 hours to 14 days after reperfusion. Levels of MMPs and TIMPs were measured by zymography and reverse zymography, respectively, in contiguous tissues. Other rats had water and electrolytes measured at 3, 24, or 48 hours after reperfusion. Treatment with a synthetic MMP inhibitor, BB-1101, on BBB permeability and cerebral edema was studied. RESULTS: Brain sucrose uptake increased after 3 and 48 hours of reperfusion, with maximal opening at 48 hours and return to normal by 14 days. There was a correlation between the levels of gelatinase A at 3 hours and the sucrose uptake (P<0.05). Gelatinase A (MMP-2) was maximally increased at 5 days, and TIMP-2 was highest at 5 days. Gelatinase B and TIMP-1 were maximally elevated at 48 hours. The inhibitor of gelatinase B, TIMP-1, was also increased at 48 hours. Treatment with BB-1101 reduced BBB opening at 3 hours and brain edema at 24 hours, but neither was affected at 48 hours. CONCLUSIONS: The initial opening at 3 hours correlated with gelatinase A levels and was blocked by a synthetic MMP inhibitor. The delayed opening, which was associated with elevated levels of gelatinase B, failed to respond to the MMP inhibitor, suggesting different mechanisms of injury for the biphasic BBB injury.     

Neuron-specific enolase concentrations in blood as a prognostic parameter in cerebrovascular diseases

BACKGROUND AND PURPOSE: To investigate the clinical relevance of plasma concentrations of neuron-specific enolase (NSE) in patients with severe cerebrovascular diseases, serial analyses were performed during the first 10 days after the acute event. METHODS: Plasma samples taken from 61 patients (30 with brain infarction, 13 with intracerebral hemorrhage, 11 with cardiogenic hypoxia-ischemia, and 7 with myocardial infarction [as control group]) were analyzed for NSE concentration using an enzyme immunoassay. The time course of plasma NSE was correlated with clinical findings, clinical outcome, cranial computed tomography, intracranial pressure, and other laboratory data. RESULTS: In cases of hypoxia-ischemia there was close correlation between plasma NSE values during the first 72 hours and the clinical outcome. In brain infarction and intracerebral hemorrhage, high plasma NSE mostly indicated an unfavorable outcome, but low values did not permit a reliable prognostic estimation. In cases of cerebral infarction and intracerebral hemorrhage with secondary neuronal destruction (for example, due to malignant edema), increasing NSE concentrations in plasma preceded the change of clinical or other diagnostic parameters. CONCLUSIONS: The course of plasma NSE levels is seen as a relevant parameter for assessing the prognosis of cerebral hypoxia-ischemia. Additionally, it may prove to be a useful tool for monitoring space-occupying brain infarctions and intracerebral hemorrhages and therefore may contribute to improved therapeutic management of severe cerebrovascular diseases.     

Enolic iridolactone and other iridoids from Alberta magna

OBJECT: The mechanisms of brain edema formation following spontaneous intracerebral hemorrhage (ICH) are not well understood. In previous studies, no significant edema formation has been found 24 hours after infusion of packed red blood cells (RBCs) into the brain of a rat or pig; however, there is evidence that hemoglobin can be neurotoxic. In this study, the authors reexamined the role of RBCs and hemoglobin in edema formation after ICH. METHODS: The experiments involved infusion of whole blood, packed RBCs, lysed RBCs, rat hemoglobin, or thrombin into the right basal ganglia of Sprague-Dawley rats. The animals were killed at different time points and brain water and ion contents were measured. The results showed that lysed autologous erythrocytes, but not packed erythrocytes, produced marked brain edema 24 hours after infusion and that this edema formation could be mimicked by hemoglobin infusion. Although infusion of packed RBCs did not produce dramatic brain edema during the first 2 days, it did induce a marked increase in brain water content 3 days postinfusion. Edema formation following thrombin infusion peaked at 24 to 48 hours. This is earlier than the peak in edema formation that follows ICH, suggesting that there is a delayed, nonthrombin-mediated, edemogenic component of ICH. CONCLUSIONS: These results demonstrate that RBCs play a potentially important role in delayed edema development after ICH and that RBC lysis and hemoglobin toxicity may be useful targets for therapeutic intervention.     

Increase in endocervical CD4 lymphocytes among women with nonulcerative sexually transmitted diseases

BACKGROUND AND PURPOSE: Stroke-prone spontaneously hypertensive rats (SHRSP) subjected to high sodium intake develop severe hypertension, cerebral edema, and proteinuria, culminating in organ damage and early death. MRI, which can be applied serially, provides the unique opportunity to study temporal and quantitative relations between these changes and whether diminution of sodium intake can attenuate established cerebral edema. METHODS: SHRSP were subjected to 1% NaCl in drinking water. Cerebral MRI, proteinuria and systolic blood pressure (SBP) were measured serially. After detection of cerebral edema (T2-weighted MRI), 6 rats were killed for histology, to confirm the diagnosis of cerebral edema. The others were followed up for 7 more days while salt loading was continued (n = 10, group 1) or after sodium intake was normalized (n = 7, group 2). RESULTS: SHRSP invariably developed cerebral edema in 30 days (range, 8 to 54 days). At this point neurological signs were absent in 16 of 23 rats. SBP rose until 1 week before detection of cerebral edema, and then stabilized at approximately 265 mm Hg. Proteinuria invariably preceded cerebral edema, with a concentration exceeding 40 mg/d predicting development of cerebral edema in 9 days (range, 3 to 15 days). There was linear correlation (R=.62, P<.0001) between proteinuria and cerebral edema (pixels with an intensity above a defined threshold). Rats in group 1 showed an increase in cerebral edema (from 5.8+/-1.1% to 12.5+/-2.8%; P<.05), and proteinuria remained high (from 305+/-44 to 338+/-29 mg/d); and 2 died spontaneously. Rats in group 2 showed no significant change in edema (from 4.9+/-0.5% to 6.9+/-1.3%) but a marked fall in proteinuria (from 294+/-24 to 119+/-10 mg/d; P<.05), both significantly different from group 1 (P<.05); all survived. SBP remained unaltered in both groups. CONCLUSIONS: Our data establish MRI as a sensitive method for detection of cerebral edema, often prior to neurological signs, in SHRSP. Proteinuria predicts cerebral edema, and these two variables, both obtained noninvasively, are quantitatively related. Moreover, in SHRSP normalizing sodium intake after salt loading attenuates development of cerebral edema and reduces proteinuria.     

FLAIR images of mild head trauma with transient amnesia

A newly advanced MRI pulse sequence, the FLAIR (fluid-attenuated inversion recovery) imaging, in which a long TE spin echo sequence is used with suppression of the CSF with an inversion pulse, displays the CSF space as a no signal intensity area. We examined 45 cases of mild head trauma with posttraumatic amnesia by FLAIR images and could detect some findings which could not be detected by CT scan and conventional MR images. These findings could be detected in many patients with long post-traumatic amnesia (over 2 hours), but they could not be detected in patients with short posttraumatic amnesia (within 30 mins). These findings existed surrounding lateral ventricles and we classified them into 3 types: type 1 is anterior horn of lateral ventricle, type 2 is the base of frontal lobe, type 3 is cerebral deep white matter. Some of them were examined again by FLAIR images a month later, and these findings had disappeared. We suspect that these lesions were brain edema or mild contusion without hemorrhage.     

Cataract surgery combined with transpupillary silicone oil removal through planned posterior capsulotomy

OBJECTIVE: The purpose of the study was to evaluate transpupillary removal of silicone oil combined with cataract surgery in patients after pars plana vitrectomy. DESIGN: A prospective case-control study. PARTICIPANTS: Fifty consecutive patients underwent cataract surgery combined with removal of silicone oil, which had served as intraocular tamponade after pars plana vitrectomy. In 28 patients, silicone oil was removed through a planned posterior capsulotomy, and in 22 patients, silicone oil was removed through pars plana sclerotomies. All patients were operated on by the same surgeon. INTERVENTIONS: Pars plana vitrectomy, cataract surgery, and silicone oil removal were performed. MAIN OUTCOME MEASURES: Frequencies of retinal redetachment, secondary cataract, cystoid macular edema, and vitreous hemorrhage; visual acuity; intraocular pressure; and duration of surgery and visual rehabilitation were measured. RESULTS: Frequencies of postoperative vitreous hemorrhage (1 of 28 [4%] vs. 10 of 22 [45%]) and secondary cataract (0 of 28 vs. 6 of 22 [27%]) were significantly lower (P < 0.05; chi-square test), and duration of surgery and visual rehabilitation were significantly shorter (P < 0.01) for patients with transpupillary silicone oil removal than for patients with drainage of silicone oil through pars plana sclerotomies. Rate of retinal redetachment (4 of 28 [14%] vs. 4 of 22 [18%]), time of retinal redetachment (36 +/- 32 postoperative days vs. 54 +/- 65 days), frequency of dislocated intraocular lenses (1 of 28 vs. 0 of 22), and postoperative visual acuity did not vary significantly between the two groups. Persisting comeal endothelial decompensation and clinically significant cystoid macular edema due to cataract surgery were not observed in any patient. CONCLUSIONS: Silicone oil removal can be combined with cataract surgery. In view of a decreased frequency of postoperative vitreous hemorrhage, reduced rate of secondary cataract, and shorter duration of surgery and visual rehabilitation, transpupillary drainage of silicone oil through a planned posterior capsulotomy compares favorably with removal of silicone oil through pars plana sclerotomies. Retinal redetachment usually occurs within the first 3 postoperative months.     

Expression of matrix metalloproteinases 2 and 9 in regenerating skeletal muscle: a study in experimentally injured and mdx muscles

Matrix metalloproteinases (MMPs) cooperatively degrade all components of the extracellular matrix (ECM). Remodeling of ECM during skeletal muscle degeneration and regeneration suggests a tight regulation of matrix-degrading activity during muscle regeneration. In this study, we investigated the expression of MMP-2 and MMP-9, in normal muscles and their regulation during regeneration process. We further investigated their secretion by C2C12 myogenic cell line. Two models of muscle degeneration-regeneration were used: (1) normal muscles in which necrosis was experimentally induced by cardiotoxin injection; (2) mdx muscles which exhibit recurrent signs of focal myofiber necrosis followed by successful regeneration. MMPs were studied by zymography; their free activity was quantified using 3H-labeled gelatin substrate and mRNA expression was followed by Northern hybridization. Muscle degeneration-regeneration was analyzed by conventional morphological methods and in situ hybridization was performed on muscle sections to identify the cells expressing these MMPs. Results show that MMP-2, but not MMP-9 expression, is constitutive in normal muscles. Upon injury, the active form of MMP-2 is transiently increased, whereas MMP-9 is induced within 24 h and remains present for several days. Quantitative assays of free gelatinolytic activity show a progressive and steady increase that culminates at 7 days postinjury and slowly returns to normal levels. In adult mdx mice, both pro and active forms of MMP-2 and MMP-9 are expressed. Northern blot results support these findings. Zymography of C2C12-conditioned medium shows that myogenic cells produce MMP-2. By in situ hybridization we localized MMP-9 mRNA in inflammatory cells and putative activated satellite cells in injured muscles. Our data allow the correlation of the differential expression of pro and/or active forms of MMP-2 and MMP-9 with different stages of the degeneration-regeneration process: MMP-9 expression is related to the inflammatory response and probably to the activation of satellite cells, whereas MMP-2 activation is concomitant with the regeneration of new myofibers.     

Edema associated with I-125 or Pd-103 prostate brachytherapy and its impact on post-implant dosimetry: an analysis based on serial CT acquisition

PURPOSE: To characterize the magnitude and duration of post-implant edema following the implantation of I-125 or Pd-103 seeds into the prostate and to investigate its effect on the CT-based calculation of the total dose delivered by the implant. MATERIALS AND METHODS: A pre-implant CT scan and 3 to 5 serial post-implant CT scans were obtained on 10 patients who received either I-125 or Pd-103 seed implants. None of the patients received hormone therapy. The magnitude and duration of edema were determined from the change in the spatial distribution of the implanted seeds as the edema resolves. Dose volume histograms were compiled to determine the percentage of the prostate volume that received a dose equal to, or greater than, the prescribed dose. RESULTS: The magnitude of the edema, expressed as the ratio of the post- to pre-implant volume on the day of the procedure, ranged from 1.33 to 1.96 (mean 1.52). The edema decreased exponentially with time; however, the edema half-life (time for the edema to decrease by 1/2) varied from 4 to 25 days (mean 9.3 days). As the edema resolved, the percentage of the prostate that received a dose equal to or greater than the prescribed dose increased by at least 7% in 7 of the 10 patients and increased by more than 15% in 2. In those patients in whom dose coverage was unaffected by the resolution of edema, more than 90% of the prostate was covered by the prescribed dose in the initial CT scan. CONCLUSION: Post-implant edema increased the prostate volume by factors which ranged from 1.33 to 1.96 (mean: 1.52). The edema resolved exponentially with an edema half-life which varied from 4 to 25 days (mean: 9.3 days). Edema had a significant effect on the post-implant dosimetry in 7 of 10 cases. Factors that affect the impact of edema on the dosimetry are the magnitude of the edema and the planned margin between the prescribed isodose line and the periphery of the prostate.     

Diagnosing pregnancy in free-ranging elk using fecal steroid metabolites

We validated fecal metabolite analysis as a noninvasive means of diagnosing pregnancy in uncaptured, free-ranging Rocky Mountain elk (Cervus elaphus nelsoni). During November 1991, we collected blood samples from 21 radiocollared, 1- to 10-year-old female elk in Yellowstone National Park, Wyoming (USA), and determined their pregnancy status by radioimmunoassay of serum pregnancy specific protein B and serum progesterone concentrations. From December 1991 through April 1992, we collected three to 12 fecal samples from each collared elk and measured the concentration of estrone conjugates, pregnanediol-3-glucuronide, and free progesterone by enzyme immunoassays. We also evaluated fecal samples from 10 unmarked male and eight calf elk. Pregnant females had significantly (P < 0.001) higher concentrations of all three fecal metabolites than nonpregnant animals, especially later in gestation (March to April). We developed all possible combinations of univariate, bivariate, and multivariate discriminant function analysis models to determine those variables most useful in predicting memberships of pregnant versus nonpregnant elk during the March to April time-period. We validated each model by applying the classification functions to 11 pregnant and eight nonpregnant elk that were not included in the development of the original models. Accuracy of the discriminant function analysis models ranged from 57 to 84%, with the univariate model based on pregnanediol-3-glucuronide concentration providing the highest classification. Fecal metabolite analysis will enable biologists to noninvasively assess the pregnancy status of elk, especially when diagnoses are based upon multiple samples collected between mid-March and mid-April.     

Risks of anticoagulation therapy after experimental corticectomy in the rat

To determine the optimal postoperative interval after which heparin therapy can be safely initiated, a rat model for experimental craniotomy and corticectomy was developed. In 50 rats (100 lesions), heparin therapy was initiated 1, 2, 3, 5, or 7 days after standardized bilateral frontal corticectomy and was continued for 7 days. Intraperitoneally administered heparin, 75 to 100 U/kg.h, was continuously given to maintain the activated partial thromboplastin time in one of two ranges: therapeutic (1.5-3 times control) or supratherapeutic (> 3 times control). The size of intracranial hemorrhage was determined from coronal brain sections by automated image analysis. No significant hemorrhage was observed in control (saline infusion) animals or in rats receiving therapeutic doses of heparin beginning more than 24 hours after surgery. Small (10-50 mm3) and large (> 50 mm3) hemorrhages were frequent at all intervals up to 5 days in animals with supratherapeutic activated partial thromboplastin time (P < 0.01). Judicious heparin therapy may be safely initiated at 48 hours after craniotomy and corticectomy in rats, whereas supratherapeutic anticoagulation is associated with intracranial hemorrhage at intervals of up to 5 days.     

Renal stone disease in children

Single dose intravenous toxicity studies of T-3762, a novel parenteral quinolone antimicrobial agent, were conducted in rats, dogs and monkeys. The following results were obtained. 1. In the rat study, all males and females given 260 mg/kg survived and all males and 3 of 5 females given 391 mg/kg died. Approximate lethal doses in male and female rats were between 260 and 391 mg/kg. In survived animals, decrease in locomotor activity and irregular respiration were observed. These clinical signs were recovered within 1 hour after dosing. In female rats given 260 mg/kg, no abnormalities were observed in general signs. In dead animals, decrease in locomotor activity, irregular respiration, staggering gait and tonic convulsion were observed and died within about 90 minutes after dosing. Macroscopic examinations in dead animals showed dark red discoloration in lung and had white foamy liquid in trachea. In histopathological examinations of dead animals, congestion, hemorrhage and edema were observed in lung. 2. In the dog study, 2 animals given 260 mg/kg survived and 2 animals given 521 mg/kg died. Approximate lethal dose in dogs was between 260 and 521 mg/kg. In the 260 and 521 mg/kg groups, decrease in locomotor activity, lateral position, vomiting, salivation and decrease in body temperature were observed. In the 521 mg/kg group, one animal died at 4 minutes and another 7 days after dosing. Histopathological examinations in 2 dead animals showed congestion or hemorrhage in heart, lung, liver, kidney, spleen and digestive tract. Erosion and necrosis at cartilage layer and cluster of chondrocyte were observed in scapular fossa and head of humerus in the 260 and 561 mg/kg groups. 3. In the monkey study, 2 animals given 260 mg/kg survived and 2 animals given 520 mg/kg died. Approximate lethal dose in monkeys was between 260 and 520 mg/kg. In the 260 mg/kg group, soft feces was observed. In the 520 mg/kg group, paleness mucosa of oral cavity, muscle weakness, mydriasis and dyspnea were observed and animals died within 4 minutes after dosing. Macroscopic and histopathological examinations in 2 dead animals showed congestion in lung, liver and kidney.     

Surgical care in space

Multiple malignant gliomas are relatively uncommon, but are sometimes difficult to differentiate from multiple metastatic brain tumors. We analyzed the MR findings of four cases of multiple gliomas, comparing them with 12 cases of multiple metastatic brain tumors. All tumors were pathologically proven by surgical operation or autopsy. Gliomas were located in the deep white matter of the cerebrum, with none found in the posterior fossa. Tumors were relatively large, and irregular, thick, ring-like enhancement was noted after the administration of Gd-DTPA. Intratumoral hemorrhage was noted in only one case. High signal intensity on T2WI around the tumor suggested that edema was greater and more extensive than in metastatic tumors and was seen even in the corpus callosum. One autopsied case that showed this high intensity presented not only edema but also tumor infiltration. Metastatic tumors were located mainly in the corticomedullary junction of the brain. They were relatively small, and eight of 12 tumors showed, nodular or smooth ring-like enhancement. Intratumoral hemorrhage was noted in four cases. Edema was noted mainly around the tumor. We conclude that differential diagnosis between gliomas and metastases is possible to some extent by MRI.