The predictability of corneal flap thickness and tissue laser ablation in laser in situ keratomileusis.

OBJECTIVE: To evaluate the relationship between predicted flap thickness and actual flap thickness and between predicted tissue ablation and actual tissue ablation. DESIGN: Prospective, nonrandomized comparative (self-controlled) trial. PARTICIPANTS: A total of 60 patients (102 eyes) who underwent laser in situ keratomileusis (LASIK). MAIN OUTCOME MEASURES: Subtraction pachymetry was used to determine actual corneal flap thickness and corneal tissue ablation depth. Other measurements included flap diameter and keratometry readings. RESULTS: Actual flap thickness was significantly different (P < 0.0001) from predicted flap thickness. Fifteen eyes had a predicted flap thickness of 160 micrometer and a mean actual flap of 105 micrometer (standard deviation [SD], +/-24. 3 micrometer range, 48-141 micrometer). Sixty-four had a predicted flap of 180 micrometer with an actual flap mean of 125 micrometer (SD, +/-18.5 micrometer range, 82-155 micrometer). Seventeen eyes had a predicted flap of 200 micrometer, with an actual flap mean of 144 micrometer (SD, +/-19.3 micrometer range, 108-187 micrometer). In addition, we found that significantly more tissue (P < 0.0001) was ablated than predicted. Linear regression of the observed ablation on predicted ablation yielded the following relationship: actual ablation = 14.5 + 1.5 (predicted ablation). Neither flap diameter nor flap thickness were found to increase with respect to steeper corneal curvatures. CONCLUSIONS: Actual corneal flap thickness was consistently less than predicted regardless of the depth plate used; actual tissue ablation was consistently greater than predicted tissue ablation for the laser used in this study.

Collagen shield delivery of ofloxacin to the human eye.

PURPOSE: To determine the ocular penetration of ofloxacin into the anterior chamber of the human eye when delivered by a presoaked collagen shield. SETTING: University of Colorado School of Medicine, Denver, Colorado. METHODS: This prospective randomized clinical study comprised 31 patients having cataract surgery. Patients were divided into 2 groups: the first received 3 preoperative drops of commercially available topical ofloxacin 0.3% given 10 minutes apart; the second had a collagen shield soaked in the same medication applied to the eye before surgery. Aqueous humor was extracted immediately before surgery for analysis. RESULTS: Mean aqueous concentration was 287 ng/mL +/- 69 (SEM) (range 40 to 1141 ng/mL) in the drops group and 957 +/- 189 ng/mL (range 214 to 2437 ng/mL) in the shield group. The difference was statistically significant (P < .005). The minimum inhibitory concentration (MIC) for selected ocular pathogens is between 500 and 4000 ng/mL. CONCLUSIONS: A collagen shield presoaked in commercially available topical ofloxacin and applied before surgery appears safe. The MICs for many common ocular pathogens were reached or exceeded. Further study is recommended to determine whether this method of infection prophylaxis is an acceptable substitute for subconjunctival injections of antibiotics.

Evaluating applicants to emergency medicine residency programs.

This article reviews the pertinent literature related to the selection process of medical students to emergency medicine residency programs. The impact that academic performance in medical school, the interview, letters of recommendation, and other achievements have on the performance of the future resident are reviewed. All articles identified by an English language MEDLINE search were reviewed by the authors as to significance to the subject. Review of relevant literature indicates that no precise correlation can be made between performance in medical school and achievements during the residency, although there seems to be a correlation between academic performance in medical school and similar performance on board certification examinations.

Effect of 50 milliliters of 50% dextrose in water administration on the blood sugar of euglycemic volunteers.

OBJECTIVE: To evaluate the effect of administration of 1 ampule of 50% dextrose in water solution (D50W) on serum glucose levels in healthy adult volunteers, the authors set out to determine whether a pre-D50W serum glucose level can be predicted from the ED sample. METHODS: This was a prospective, interventional study conducted from the ED of an urban, university-affiliated hospital. All subjects were healthy employee volunteers between 25 and 40 years of age. Baseline serum glucose levels were determined and all subjects were given an i.v. bolus of 25 grams of 50% dextrose solution. The main outcome measures were post-D50W serum glucose levels (observed) at 5 predetermined time intervals (5 min, 15 min, 30 min, 1 hr, and 2 hr). An expected change in serum glucose was calculated using the volume of distribution formula for glucose. RESULTS: Twenty-five volunteers (17 males and 8 females) participated in the study. The mean baseline serum glucose was 82.3 +/- 13.5 mg/dL. The mean post-infusion levels were: 244.4 +/- 44.6 mg/dL (5 min), 145.8 +/- 52.3 mg/dL (15 min), 88.1 +/- 28.8 mg/dL (30 min), 77.6 +/- 13.6 mg/dL (60 min), and 83.2 +/- 11.4 mg/dL (120 min). Using a mixed-effect regression model, statistically significant increases in serum glucose levels were found at 5 minutes (p < 0.001) and 15 minutes (p < 00001) following administration of D50W. There was a return to baseline serum glucose by 30 minutes. The expected change based on the volume of distribution formula (53.7 +/- 34.9) did not correlate with the observed changes at any measured time interval. CONCLUSION: Without pre-intervention blood drawing by emergency medical services, it is not possible to accurately predict pre-D50W serum glucose levels based on post-D50W glucose levels. The diagnosis of hypoglycemia as the etiology of altered mental status must therefore remain a diagnosis of exclusion. In addition, the return of serum glucose to baseline after 30 minutes suggests the duration of the effect of 1 ampule of D50W. Frequent re-evaluation of the serum glucose levels of suspected or proven hypoglycemic patients after administration of D50W should be considered.

Emergency department do-not-attempt-resuscitation orders: next-of-kin response to the emergency physician.

OBJECTIVE: To evaluate the response by families of incompetent, chronically debilitated, and/or terminally ill patients who were contacted for do-not-attempt-resuscitation (DNAR) status by an emergency physician (EP). METHODS: A prospective observational study was performed to assess next-of-kin willingness to support DNAR status for incompetent, chronically debilitated, and/or terminally ill patients. The families also were contacted by telephone follow-up 48-72 hours after the ED visit. Upon follow-up evaluation, the families were surveyed regarding prior DNAR instructions and their perceptions of the establishment of DNAR status in the ED. The study was conducted in an urban teaching hospital with an emergency medicine residency training program. RESULTS: Of the 71 patient families contacted, 60 (85%) of the patients had DNAR orders written in the ED. The families of these 60 patients had no negative response regarding contact by ED personnel. Of the 11 (15%) patients whose families wished no DNAR order, only two families had negative responses to being contacted by the EP. In both cases the families had previously given detailed instructions to the chronic care facility. CONCLUSION: The EP can play an important role in assisting the decision making process of families of incompetent, chronically debilitated, and/or terminally ill patients regarding institution of DNAR orders in the ED. Improved communication regarding existing DNAR orders with chronic care facilities might minimize the rare complaints received from families with preestablished DNAR orders.

Cyproheptadine-induced central anticholinergic syndrome in a child: a case report.

A 16-year-old female patient presented to our emergency department with anticholinergic psychosis after an ingestion of cyproheptadine. The central anticholinergic syndrome occurs frequently but often goes unrecognized because many patients do not fit into a well defined clinical pattern. The diagnosis depends on the suspicion and recognition of the psychiatric manifestations, including agitation, confusion, and hallucinations. A high index of suspicion is necessary in children in particular, since central effects seem to predominate in many anticholinergic overdoses.

Anterior spinal artery infarction.

Spinal cord ischemia, as represented by acute paraplegia, is rare in the absence of trauma. It is even more uncommon that an infarction of the spinal cord occurs in a patient with no predisposition to vascular disease. We report a case of anterior spinal artery syndrome resulting from an infarction of the anterior aspect of the spinal cord in an otherwise healthy 45-year-old woman.

Residents' attitudes toward the legal system and court testimony in child abuse.

Resident physicians' contacts with the legal system during management of abused children may influence their attitudes, which were evaluated in a pilot survey completed by 42 pediatric and medicine/pediatric residents. Although negative attitudes toward attorneys were common, almost all of the residents considered general and hearing-specific legal training to be a legitimate part of their residency program. They reported lower levels of stress of court testimony than expected by the authors. Most who had testified in court believed their testimony had been needed and helpful, but all who believed their testimony had been a waste of time were senior-level residents. Although most residents believed the laws and courts usually work for protecting children, only 8 of the 20 residents who had previously testified in court responded affirmatively, and none of the 10 senior residents who had previously testified held this belief. The disillusionment of senior-level residents appeared to affect attitudes toward patient care less than expected, in that 90% of those who planned to enter private practice indicated they would perform physical abuse evaluations and 70% planned to perform sexual abuse evaluations. Only one resident who did not expect to perform the evaluations gave as a reason the prospect of having to testify in court.

Clinical, pathological, and biochemical studies on an infantile case of sulfatide/GM1 activator protein deficiency.

A 28-month-old black male died with severe complications of mental and motor deterioration, seizures, and aspiration. Autopsy demonstrated moderate liver enlargement, normal spleen and kidneys, small testes, and a grossly normal brain. Further examination showed irregular macrogyrae with evidence of a storage or sclerotic process. Thin layer chromatography of the lipids in formalin-fixed tissue demonstrated elevated levels of ceramide trihexoside and possibly sulfatides in liver and a decrease in the ratio of galactosylceramide to sulfatide in brain. Examination of the gangliosides in formalin-fixed brain indicated a slight increase in the percentage of GM1 ganglioside and a clear elevation in GM2 and GM3 gangliosides. Cultured skin fibroblasts had a normal activity for a large number of lysosomal enzymes including arylsulfatase A and galactocerebrosidase. When the cells were loaded with [14C]sulfatide only about 12% of the sulfatide was metabolized after 3 days. Extracts of the cells were subjected to SDS-PAGE and immunoblotting with antisphingolipid activator protein-1 (SAP-1) rabbit antiserum, and no cross-reacting material was detected confirming the diagnosis of metachromatic leukodystrophy caused by SAP-1 deficiency. This patient was clinically more severe than the other patients described previously with this deficiency. Further studies are underway to define the nature of the mutation in this patient.

Spinal cord trauma: in search of the meaning of granular axoplasm and vesicular myelin.

The rapid appearance of selective axonal calcification following experimentally induced spinal cord impact injury has suggested that there is a sudden influx of intracellular calcium which mediates many of the pathological changes subsequent to the trauma. Granular dissolution of axoplasm and vesicular disruption of myelin are the most characteristic alterations in the affected white matter. These changes, which appear early and progress, are identical to those that can be induced by exposing myelinated axons to increased extracellular calcium or to calcium ionophores. These observations have led us to develop the hypothesis that calcium mediates the destruction of traumatized axons in the spinal cord by stimulating calcium-activated neutral proteinases (CANP), which in turn degrade axonal and myelin proteins. A rapid increase in CANP activity has been demonstrated in our experimental rat trauma model and a CANP has been isolated from rat spinal cord myelin which degrades both neurofilament and myelin proteins. However, the interpretation of the role of calcium has been complicated by the fact that granular axoplasm and vesicular myelin can be induced under conditions other than those favorable for CANP enhancement. The ultimate proof of the calcium hypothesis will depend on analyzing early intracellular ionic fluxes and correlating these with the localization of calcium-mediated enzymes and the evolution of pathological events.

In vitro spinal cord trauma.

Fetal mouse spinal cord explants were harvested and allowed to grow in Maximow chambers. Normal appearing matured cultures were subjected to a brief episode of impact trauma by dropping the flat surface of 25 to 105 mg dressmaker's pins from a height of 10 cm directly onto the exposed surface of the culture. Light and electron microscopic studies at selected posttrauma intervals revealed discrete foci of necrosis preceded or accompanied by nerve fiber changes (granular axoplasm, vesicular myelin, pleomorphic spheroids) identical with those documented in spinal cord trauma in vivo. Although no inherent calcification was observed, calcium was added to some of the traumatized cultures and it was subsequently localized by pyroantimonate in the axoplasm; within mitochondria, adjacent to neurofilaments, and in the cytosol. The study indicates that the morphologic sequence of events of spinal cord trauma in vitro are similar to those observed in vivo, and that the latter may occur in the absence of vascular injury.

Brain calcium content in ischemic infarction.

Three degrees of focal ischemic infarction in the rat were created in the cerebral cortex supplied by the right middle cerebral artery, by ligation of the right middle cerebral artery and the right common carotid artery and temporary clip compression of the left common carotid artery, in succession. The postischemic accumulation of calcium in cerebral cortex of the right middle cerebral artery territory, determined by atomic absorption spectrometry, correlated with the infarct volume. The results are consistent with the hypothesis that calcium has role as a mediator in the pathogenesis of cerebral infarction.

Myelopathy induced by lactic acid.

This study defines the conditions required to provoke myelopathic changes by dripping lactic acid onto the surgically exposed spinal cord of adult male rats. A severe necrotizing myelopathy was observed after 24 h, principally in the posterior half of the cord at the level of lactic acid (pH 1.8) application. A profound early effect on small blood vessel walls, appearing necrotic after 30 min to 2 h, was identified. Nerve fiber alterations (axonal stasis, granular axoplasm, axonal calcification, and vesicular myelin), identical to those appearing early in the myelopathies of trauma and calcium toxicity, were apparent. However, the pathogenesis of these alterations in this model remains unclear, because of the vascular events and the presumed alterations of calcium metabolism by the acid. Further studies are required to elucidate the precise mechanisms of these important reactions of myelinated axons to the injuries provoked by acid, calcium, and trauma.

A model of focal ischemic stroke in the rat: reproducible extensive cortical infarction.

In the search for a more reproducible focal ischemic stroke model in the rat, we systematically interrupted blood flow to the right middle cerebral artery territory by ligating the right middle cerebral artery, and the right and left common carotid arteries in succession. Using a laser-Doppler flowmeter, we found that the relative surface blood flow in cerebral cortex supplied by the right middle cerebral artery decreased to 62, 48, and 18% of baseline respectively after successive ligation of the right middle cerebral artery, and the right and left common carotid arteries. A focal infarct in the cerebral cortex supplied by the right middle cerebral artery was consistently noted after ligation of the right middle cerebral and the right common carotid arteries and temporary clip occlusion of the left common carotid artery for 60 min. The surface areas of infarction measured 100 +/- 6 mm2 and the maximal cross-sectional area of infarction was 10.4 +/- 1.1 mm2 (N = 10). The mortality rate was 7% (N = 70). The characteristic changes of ischemic necrosis were limited to the cortex with sparing of subcortical structures. No motor deficits occurred. Occlusion of the right middle cerebral artery alone or together with the right common carotid artery did not consistently cause gross infarction and the maximal cross-sectional area of infarction was smaller (the right middle cerebral artery, 1.7 +/- 0.8 mm2, N = 10; the right middle cerebral artery plus the right common carotid artery, 4.8 +/- 1.9 mm2, N = 10). Permanent ligation of the right middle cerebral artery and both common carotid arteries had a high mortality (60% in 3 days, N = 10).(ABSTRACT TRUNCATED AT 250 WORDS)

Evidence for glycoconjugate in nociceptive primary sensory neurons and its origin from the Golgi complex.

Glycoconjugates with terminal galactose residues were localized in rat spinal cord and spinal ganglia using lectin-HRP conjugates of Griffonia simplicifolia and Glycine max agglutinins. Alternate staining of serial sections with HRP-labelled lectins and an antibody for substance P (SP) showed staining in identical primary sensory neurons with both methods. Similarly, lectin-reactive as well as SP-positive fibers were found in Rexed laminae I and II, Lissauer's tract, the spinal nucleus and tract of the trigeminal nerve, the nucleus commissuralis and a small bundle of fibers just ventral to the central canal. Administration of capsaicin to neonatal rats produced a significant decrease in lectin-reactive fibers of the substantia gelatinosa, and in the number of lectin-reactive sensory neurons. The coexistence of SP with galactose-containing glycoconjugates in spinal ganglion neurons, as well as sensitivity of these cells to capsaicin, provided a basis for classifying the reactive neurons as nociceptive in type. Ligation of dorsal roots resulted in disappearance of lectin reactivity in the spinal cord and caused accumulation of lectin-positive material proximal to the ligature, indicating somatofugal transport of galactose-containing glycoconjugates. Colchicine injection caused an increase in SP reactivity in dorsal ganglion neurons but no change in lectin staining of galactoconjugate. At the ultrastructural level affinity for the lectin conjugates was confined to the Golgi cisternae and the plasmalemma of B-type sensory neurons in the dorsal ganglion. The axolemma of unmyelinated processes stained selectively in dorsal roots and the substantia gelatinosa of the spinal cord. These findings provide evidence for the presence in certain sensory cells of a characteristic galactosylconjugate which may prove to be of significance in nerve function.

Histochemical localization of galactose-containing glycoconjugate at peripheral nodes of Ranvier in the rat.

Lectin-horseradish peroxidase conjugates were used to study glycoconjugates in paraffin sections of dorsal roots of the rat spinal cord. Griffonia simplicifolia-B4 isolectin (GSA I-B4) and peanut agglutinin (PNA) stained strongly the nodes of Ranvier, localizing, respectively, terminal alpha- and beta-D-galactose. Sialidase digestion did not increase staining with PNA at the node of Ranvier, suggesting the presence of a neutral glycoconjugate. Staining of the nodal but not the internodal axolemma was observed with PNA. The outer surface of the myelin sheath in axons of the dorsal root stained strongly with GSA I-B4 but only weakly with PNA, demonstrating an abundance of terminal alpha-galactose. PNA staining was enhanced in this site by sialidase digestion, showing terminal sialic acid-beta-galactose dimers. The presence of sialic acid here was further evidenced by labeling of these membranes with the lectin derived from the slug, Limax flavus (LFA). Affinity for a high iron diamine-Alcian blue (pH 2.5) sequence demonstrated, in addition, the presence of sulfate esters in glycoconjugates on the outer myelin membrane. GSA I-B4 imparted strong reactivity to nonmyelinated fibers in the dorsal root and the spinal nerve. The present findings appear to reflect several localizations of biochemically described nervous system glycoproteins containing O-glycosidically linked side chains terminated by alpha- and beta-D-galactose.

Orthostatic hypotension with brainstem tumors.

Three patients with brainstem tumors had orthostatic hypotension as the major presenting manifestation. Two patients had primary tumors that involved the dorsal medulla, pons, and rostral spinal cord; one was a malignant astrocytoma and the other a hemangioblastoma. The third patient had an oat cell carcinoma of the lung with subependymal spread to the medulla, pons, hypothalamus, and thalamus. Evaluation of baroreceptor function in the patient with the malignant astrocytoma showed a defect in the efferent sympathetic limb of the baroreceptor reflex arc.