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Biomedical subjects

L R Schultz

Publications and source records attributed to L R Schultz.

At least 37 records · Page 2Linked to original sources

A reproducible model of middle cerebral infarcts, compatible with long-term survival, in aged rats.

BACKGROUND AND PURPOSE: Stroke is a disease associated with aging, but experimental stroke studies are generally done in young male animals. Because there are numerous differences associated with aging, such as an altered immune system and altered neurochemistry, that could affect the outcome of these experiments, a model of reproducible cerebral infarction in aged rats is needed. METHODS: We attempted to produce middle cerebral artery (MCA) infarcts in aged (22 months of age) rats using two standard methods. A nylon suture with a heat-induced bulb was passed through the external carotid artery in seven animals, with an attempt to place the tip at the origin of the MCA. The MCA was ligated through a craniotomy just proximal to the internal cerebral vein in 14 rats. Survival potential was tested by attempting 2-week survival in four rats and 2-month survival in one rat. RESULTS: The suture model failed to produce MCA infarcts, even when the bulb of the suture was properly placed in the MCA. The intracranial MCA occlusion resulted in reproducible MCA infarcts. There were no deaths, including the animals allowed to survive 2 weeks and 2 months. CONCLUSIONS: We conclude that reproducible MCA infarcts can be produced in aged rats by craniotomy and that these lesions may be compatible with long-term survival. This should be a useful technique for studying therapeutic interventions and rehabilitation strategies in an animal model that immunologically and neurochemically more closely resembles humans at risk for stroke.

Aging↗

Post-ischemic brain tissue alkalosis suppressed by U74006F.

We monitored chronically (for 1 week) the effect of the 21-aminosteroid U74006F, a potent lipid peroxidation inhibitor, on the pH profile of the rat brain following transient forebrain ischemia. Eight rats were treated initially with 3 mg/kg i.v. of U74006F 1 min after reperfusion. A second dose of 1.5 mg/kg i.v. was given 60 min after reperfusion. A vehicle group (n = 9) was treated in the same manner, using the same volume of the vehicle solution, 20 mM citric acid, 3 mM sodium citrate, and 8 mM NaCl. Statistically significant interaction between group and time (P = 0.003) was detected for pH. Brain pH of the vehicle treated animals were significantly higher than the U74006F treated group at 24 h (P = 0.009) and 48 h (P = 0.009) of reperfusion. Chronic post-ischemic brain tissue alkalosis at 24 h (pH 7.22 +/- 0.12) and 48 h (pH 7.25 +/- 0.11) post-ischemia, observed among the vehicle treated animals (and untreated animals), was suppressed by treatment with U74006F. These results suggest a coupling between post-ischemic brain tissue alkalosis and free radical induced lipid peroxidation.

Alkalosis↗

Embolic infarcts of carotid origin differ in size and site with contralateral carotid patency.

Carotid emboli cause small infarcts in the ipsilateral hemisphere in rats when the contralateral carotid artery is fully patent. With contralateral carotid occlusion, embolic infarcts, both large and small, occur with equal proportions in both hemispheres. To determine if emboli also cross to the territory of a stenotic carotid artery, we combined high grade (78-96%) stenosis of the left common carotid artery with photochemically-induced (laser irradiation 632 nm, 200 mW/cm2, 15 min; intravenous Photofrin II, 12.5 mg/kg) embolism from the right common carotid artery in 12 rats. Ninety-eight cerebral infarcts occurred in 9 experimental animals, with eight infarcts being large (> 2.5 mm). The mean proportions of infarcts and emboli on the left were 25% and 19%, respectively. These results suggest that contralateral carotid artery stenosis, like occlusion, will influence the site and size of embolic infarcts and that the "symptomatic" carotid artery cannot always be determined by the side of the cerebral infarct.

Animals↗

Giant cell fibroblastoma with dermatofibrosarcoma protuberans-like transformation.

A giant cell fibroblastoma (GCF) presented in the subcutis of the breast in a 13-month-old girl which recurred 6 years later as a dermal and subcutaneous neoplasm whose patterns were in part GCF and spindle cells with a storiform configuration resembling dermatofibrosarcoma protuberans (DFSP). The issue remains unsettled as to whether GCF is the juvenile variant of DFSP, but an argument about this relationship is supported circumstantially by a case such as ours.

Breast Neoplasms↗

Acute elevation and recovery of intracellular [Mg2+] following human focal cerebral ischemia.

We used 31P magnetic resonance spectroscopy (MRS) to investigate changes in brain intracellular [Mg2+] following human focal cerebral ischemia. Mean brain pMg (where pMg = -log[Mg2+]) was significantly lower in the ischemic focus of all stroke patients (pMg = 3.34 +/- 0.28, n = 45, p < 0.01) when compared with normal controls (pMg = 3.50 +/- 0.08, n = 25). Ischemic brain pMg was also significantly reduced when the pH of the stroke region was acidotic (pH < 6.90, pMg = 3.07 +/- 0.44, n = 11, p < 0.01) and when the phosphocreatine index (PCrI = PCr/[PCr+Pi (inorganic phosphate)]) was reduced (PCrI < 0.47, pMg = 3.12 +/- 0.42, n = 13, p < 0.01). Mean brain pMg was significantly reduced at days 0 to 1 (acute) poststroke (pMg = 3.32 +/- 0.28, n = 26, p < 0.01) and at days 2 to 3 (subacute) poststroke (pMg = 3.38 +/- 0.28, n = 21, p = 0.03). There was also a significant (p < 0.01) correlation between decreased pMg and increased relative signal intensity of Pi (normalized by total phosphate signal, Pi/TP) for all stroke groups studied. During the temporal evolution of stroke, pH returned to normal levels by days 2 to 3, and pMg returned to normal by days 4 to 10 (subacute). PCrI and Pi/TP returned toward normal levels after 10 days (chronic), at a time when ischemic brain pH had become significantly alkalotic (pH = 7.10 +/- 0.24, n = 15, p < 0.01). Elevation of ischemic brain [Mg2+] is temporally linked to the acidotic phase of human stroke as well as the breakdown of energy metabolism. These acute changes in [Mg2+] may contribute to, or be a marker for, cellular injury.

Adenosine Triphosphate↗

Central nervous system disease in patients with systemic lupus erythematosus.

Central nervous system (CNS) dysfunction in patients with systemic lupus erythematosus (SLE) is highly variable, although it is often described under a single heading of "neuropsychiatric" or "CNS" SLE. To clarify these CNS abnormalities, we studied 91 lupus patients, 63 of whom had CNS symptoms or signs, over 599 patient years. By placing patients in relatively homogeneous clinical groups (stroke, seizure, suicide attempt, hallucination, confusion, decreased alertness) we detected significant (but variable among groups) correlations with other manifestations of SLE, suggesting separate mechanisms for each CNS disorder. These correlations were lost if all "CNS-SLE" was considered as a single group. Patients with decreased alertness often had undetected systemic infections and had a high death rate from infection, rather than from CNS-SLE. The understanding of the pathogenesis and potential treatment of CNS disorders in lupus will depend on classifying the patients into homogeneous groups.

Behavior↗

Experience with intestinal lengthening for the short-bowel syndrome.

Patients with the short-bowel syndrome frequently develop dilated intestinal segments that may lead to impaired motility and malabsorption. Although intestinal tapering alone improves motility, the intestine can be lengthened as well. We reviewed our experience with six children undergoing intestinal lengthening to improve intestinal absorption secondary to the short-bowel syndrome. The procedure was performed by dissecting the vessels along the mesenteric border and dividing the intestine longitudinally with a stapler. Five patients were receiving total parenteral nutrition (TPN) and one was becoming malnourished with enteral feedings alone. Bacterial overgrowth was documented in four patients and abnormal liver function in three patients. The intestinal segments were dilated up to 10 cm in diameter and remnant length ranged from 15 to 79 cm. Segments 5 to 25 cm in length were divided, resulting in an average increase in length of 52%. Necrosis of one of the divided limbs necessitated resection in one patient. Follow-up ranged from 2 to 84 months. TPN has been discontinued in four patients and avoided in another. Symptomatic improvement occurred in all patients. We feel the tapering and lengthening procedure should be considered in patients with symptomatic, dilated intestinal segments in whom the need for TPN may potentially be obviated.

Anastomosis, Surgical↗

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.

Administration, Intranasal↗

Oral contraceptive use may protect against low bone mass. Henry Ford Hospital Osteoporosis Cooperative Research Group.

This cross-sectional retrospective epidemiologic study investigated risk factors for low bone mineral density (BMD) in a group of 2297 women, 76% of whom were postmenopausal. Reproductive information, history of oral contraceptive use, BMD measurements, and other data were available from women presenting to 12 osteoporosis screening centers in 1986 and 1987. Each woman was classified into a BMD category based on the range of BMD measurements at her respective center. Menopause, increasing age and years since menopause, and decreasing body mass index were associated with low BMD. A history of oral contraceptive use was protective against low BMD (odds ratio = 0.35, 95% confidence interval = 0.23 to 0.53). Multivariate analyses confirmed this result and further demonstrated that increasing duration of use was protective. These data suggest that prior use of oral contraceptive agents is associated with higher levels of BMD and that the degree of protection from lower BMD is related to duration of exposure.

Adolescent↗

Cerebrovascular complications of the use of the "crack" form of alkaloidal cocaine.

BACKGROUND AND METHODS: The use of cocaine, especially one of its alkaloidal forms ("crack"), has been increasingly associated with cerebrovascular disease. To clarify the clinical, radiologic, and pathological features of the events associated with cocaine use, we identified 28 patients at four medical centers who had stroke temporally related to the use of alkaloidal cocaine (during or within 72 hours of use). RESULTS: The 28 patients had the following types of cerebrovascular event: cerebral infarction (n = 18 [2 hemorrhagic; 1 fatal]) in the areas supplied by the middle cerebral artery (n = 10), anterior cerebral artery (n = 3), posterior cerebral artery (n = 1), and vertebrobasilar arteries (n = 4); subarachnoid hemorrhage (n = 5); intraparenchymal hemorrhage (n = 4); and primary intraventricular hemorrhage (n = 1). Eighteen patients (64 percent) had acute neurologic symptoms immediately or within one hour of using cocaine. Fifteen patients (45 percent) with either occlusive or hemorrhagic strokes had sever headache as an early symptom. Vasculitis was not suggested by radiography in any patient, nor was it identified on pathological examination in one patient who died. All the patients were young (mean age, 34 years; range, 23 to 49) and had no other apparent, direct cause of stroke. Other risk factors for stroke among the patients included mild mitral-valve prolapse (n = 4), hypertension (n = 4), cigarette smoking (n = 8), and regular alcohol use (n = 6). CONCLUSIONS: There is a strong temporal association of the use of alkaloidal cocaine with both ischemic and hemorrhagic cerebrovascular events. Cocaine-related stroke probably has many causes. A thorough history focusing on the use of cocaine and toxicologic screening of urine and serum should be part of the evaluation of any young patient with a stroke.

Adult↗

Effects of cigarette smoking and propranolol in survivors of acute myocardial infarction.

The effect of propranolol on mortality and reinfarction after acute myocardial infarction (AMI) in cigarette smokers and nonsmokers was studied in the Beta Blocker Heart Attack Trial. Cigarette smokers (n = 2,332) were 5 years younger than nonsmokers and had a lower incidence of diabetes mellitus, systemic hypertension, previous AMI and cardiomegaly. Among cigarette smokers, the placebo group had a higher total mortality rate than the propranolol group (11.0 vs 7.4%, p less than 0.0008) and more sudden cardiac deaths (7.1 vs 4.6%, p less than 0.009). In nonsmokers the placebo group had a mortality (7.9 vs 7.1%, p greater than 0.64) similar to the propranolol group. After baseline adjustment, cigarette smokers were estimated to have 1.6 times the risk of dying as compared to nonsmokers (p less than 0.0007). Adjusting for baseline differences, both treatment with propranolol and nonsmoking were predictors of survival. No detectable nonsmoking/propranolol interaction could be identified. In survivors of AMI a beneficial effect of propranolol is observed for cigarette smokers. Nevertheless, cigarette smoking continues to be a risk factor for mortality after AMI even for those receiving propranolol.

Double-Blind Method↗

Risk of colorectal cancer among automotive pattern and model makers.

Twofold to threefold increases in risk for colorectal cancer associated with pattern and model making in the automobile industry have been suggested by several reports. This paper reports the investigation of a cohort of 7545 General Motors pattern and model makers originally defined for the purpose of cancer screening. All-cause mortality for this cohort was lower than that of the US population (standardized mortality ratio [SMR] = 0.7; 95% confidence limits 0.6, 0.8). There were 22 colon cancer deaths v 10.9 expected, resulting in a significantly elevated SMR of 2.0 (95% confidence limits of 1.3, 3.0), consistent with previous studies. The colon cancer SMR for nonparticipants in the screening programs was 4.0 (95% confidence limits of 2.2, 6.7), emphasizing the importance of complete follow-up for all members of a defined cohort.

Adult↗

Preliminary observations on brain energy metabolism in migraine studied by in vivo phosphorus 31 NMR spectroscopy.

We measured brain energy phosphate metabolism and intracellular pH (pHi) in a cross-sectional study of migraine patients by in vivo phosphorus 31 NMR spectroscopy. During a migraine attack the ratio ATP/total phosphate signal (mole % ATP) was preserved, but there was a decrease in mole % phosphocreatine (PCr) and an increase in mole % inorganic phosphate (Pi) resulting in a decrease of the PCr/Pi ratio, an index of brain phosphorylation potential. This was found in classic but not common migraine. Mole % Pi was also increased in combined brain regions between attacks. There was no alteration in brain pHi during or between attacks. Energy phosphate metabolism but not pHi appears disordered during a migraine attack.

Adenosine Triphosphate↗

The effects of aging on cerebral blood flow in migraine.

We studied cerebral blood flow (CBF) with the 133xenon inhalation technique in 92 migraine patients (49 classic/complicated, 43 common), aged 19 to 85 years, in the headache-free period. We compared results to 49 control subjects, aged 22 to 80 years. CBF declined with age in both groups, but at a slower rate in migraine patients, a difference most pronounced in classic migraine. CBF was lower in migraine patients than in controls under 48 years of age. In addition, regional asymmetry of blood flow was found more frequently in young migraine patients than in controls. These results suggest that differences exist in cerebrovascular resistance tone in migraine patients, which may contribute to the threshold for a migraine attack and result in differing age-related changes in blood flow.

Adult↗