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Biomedical subjects

C M Harper

Publications and source records attributed to C M Harper.

At least 19 recordsLinked to original sources
PubMed1996

MELAS- and Kearns-Sayre-type co-mutation [corrected] with myopathy and autoimmune polyendocrinopathy.

A 35-year-old woman with features of Kearns-Sayre syndrome consisting of progressive ptosis, ophthalmoparesis, mitochondrial myopathy, and pigmentary retinopathy also had autoimmune polyglandular syndrome type 11 (Addison's disease, autoimmune insulin-dependent diabetes mellitus, Hashimoto's thyroiditis, and primary ovarian failure). There was no history of similarly affected relatives. Analysis of muscle mitochondrial DNA (mtDNA) revealed a 2,532-bp deletion of the type seen in Kearns-Sayre syndrome as well as a heteroplasmic A3243G mutation in the tRNA-Leu(UUR) gene of the type seen in mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS). The patient's blood and her mother's blood harbored the A3243G mutation but not the deletion, and the maternal grandmother's blood had neither mutation. In muscle, the species of mtDNA harboring the deletion was exclusively associated with the species harboring the A3243G mutation, suggesting that the point mutation predisposed to the large-scale deletion. The mtDNA species with both mutations accounted for 88% of total muscle mtDNA. Other and as yet unrecognized point mutations in mtDNA might also be associated with, and possible causally related to, large-scale mtDNA deletions.

Adult↗
PubMed1996

Far-field auditory brainstem response in neurotologic surgery.

This is a review of our experience using far-field auditory brainstem monitoring during acoustic neuroma removal. The observations are based on 144 consecutive cases beginning in 1986. The factors of importance are tumor size, preoperative auditory function, and the preoperative presence of a wave V on the auditory brainstem response. Our experience suggests that preservation of hearing in tumors > 2.5 cm is rare. It was observed that preserving wave V does not guarantee preservation of hearing. Conversely, loss of wave V does not preclude preservation of hearing. It has also been noted that the presence of only wave I preoperatively does offer some hope that hearing can be preserved postoperatively. Finally, postoperative hearing function is usually equal to or worse than the preoperative function. Only rarely does the postoperative function improve.

Adolescent↗
PubMed1995

Pristane-induced effects on cytochrome P-4501A, ornithine decarboxylase and putrescine in rats.

The effects of pristane (2,6,10,14-tetramethylpentadecane) on cytochrome P-4501A (cP4501A) activity in microsomes, as well as on ornithine decarboxylase (ODC) activity and concomitant putrescine levels were examined in Copenhagen rats. In general, pristane treatment led to increased cP4501A levels when compared to basal levels, while co-treatment with 3-methylcholanthrene (3-MC) and pristane elicited augmented cP4501A responses when compared to responses induced by 3-MC alone. Increases in both ODC activity and putrescine levels were also observed in pristane treated rats. Collectively, these results indicate that pristane influences cP4501A activity and elicits promoter-like responses as reflected in elevated ODC activity and increased amount of putrescine.

Animals↗
PubMed1995

Treatment of stable chronic demyelinating polyneuropathy with 3,4-diaminopyridine.

OBJECTIVE: To determine whether 3,4-diaminopyridine (3,4-DAP) would improve clinical or electrophysiologic function in patients with stable chronic demyelinating polyneuropathy. DESIGN: We conducted a prospective, randomized, placebo-controlled, blinded, crossover study of 3,4-DAP in 34 patients with demyelinating polyneuropathy. MATERIAL AND METHODS: Of the 17 men and 17 women, who were 21 to 80 years of age, 27 had hereditary motor and sensory neuropathy type I and 7 had acquired demyelinating polyneuropathy. Treatment consisted of stepped doses of 3,4-DAP (increasing to 20 mg four times daily) or placebo for 4 days. Pretreatment and posttreatment determination of the Neurologic Disability Score (NDS); isometric muscle strength testing; median, ulnar, and peroneal nerve conduction studies; and measurement of serum 3,4-DAP were performed. Quantitative computer-assisted sensory examinations were done in five patients. RESULTS: The results for the final day of treatment with 3,4-DAP or placebo and the differences between pretreatment and posttreatment findings for total NDS, sensory NDS, isometric muscle strength testing, compound muscle action potential amplitude, sensory nerve action potential amplitude, motor and sensory conduction velocities, and vibration and cold detection thresholds did not vary significantly. A small improvement of 4 points in the motor NDS (P < 0.05) was found. Five patients with electrophysiologic conduction block had no significant reduction in the degree of block. CONCLUSION: Because no improvement was noted in most measurements of neurologic function, despite use of high doses of drug, 3,4-DAP is unlikely to be beneficial in the treatment of stable chronic demyelinating polyneuropathy.

4-Aminopyridine↗
PubMed1994

Recipient mononuclear cell recognition and adhesion to graft endothelium after human cardiac transplantation. Lymphocyte recognition leads to monocyte adhesion.

Transendothelial migration of mononuclear cells is crucial in the development of allograft rejection and transplant coronary disease. Adhesion of circulating cells to endothelium is the initial step in transendothelial migration. Human aortic endothelial cell cultures were established from aortic tissue harvested at the time of organ donation for cardiac transplantation which allowed specific recipient mononuclear cell-graft endothelial interactions to be studied. Confluent untreated endothelial cells were incubated with recipient mononuclear cells for 15 min to assess adhesion. Adhesion of recipient mononuclear cells to endothelium derived from their graft was threefold higher than adhesion to nonspecific endothelium (93 +/- 20 vs. 30 +/- 11 cells/high power field, P < 0.005). Graft-specific adhesion was inhibited by preincubation of the endothelium with antibodies to class I HLA (34 +/- 16 cells/high power field, P < 0.005). Immunofluorescence performed after adhesion showed that 73 +/- 6% of both specific and nonspecific adherent cells were monocytes. The use of purified lymphocyte and monocyte preparations showed that graft-specific lymphocytes induce unrelated monocytes to become adherent. These results suggest that lymphocytes are primed in vivo to recognize endothelium derived from their graft which leads to a rapid increase in lymphocyte and monocyte adhesion. Such allo-recognition may involve endothelial class I HLA molecules.

CD3 Complex↗
PubMed1993

Newly recognized congenital myasthenic syndrome associated with high conductance and fast closure of the acetylcholine receptor channel.

We describe here a new congenital myasthenic syndrome associated with a kinetic abnormality of the acetylcholine receptor (AChR) channel. The propositus had poor suck and cry after birth. Subsequently, she had intermittent ocular symptoms and fatigued abnormally on exertion. At age 9 years, significant weakness was detected only in the frontalis, levator palpebrae, and neck flexor muscles. Electromyography showed no decrement in limb muscles but single-fiber examination of the facial muscles was consistent with a neuromuscular transmission defect. The ocular symptoms responded partially to pyridostigmine, but the abnormal fatigability did not. Tests for anti-AChR antibodies were negative. A younger sister had elements of the same disease. An intercostal muscle specimen was obtained from the propositus at age 9 years for endplate studies. The quantal content of the endplate potential was normal. Miniature endplate currents were abnormally large and their decay time constant was abnormally short. AChR channel properties were studied by analysis of acetylcholine-induced current noise. The mean single-channel conductance was increased 1.7-fold and the mean channel open time was 30% shorter than normal. The number of AChR per endplate was normal. Electron microscopy of most endplates showed no abnormality, but a few were degenerating or simplified. The channel abnormality may stem from a point mutation in an AChR subunit affecting a single amino acid residue lining the pore of the AChR channel. The mechanism by which the physiological abnormality produces clinical symptoms is not known, but possible explanations are considered.

Adult↗
PubMed1993

Congenital myasthenic syndromes: I. Deficiency and short open-time of the acetylcholine receptor.

A 5.5-year-old girl had myasthenic symptoms since birth. Tests for antiacetylcholine receptor (AChR) antibodies were negative. To investigate the character of the neuromuscular transmission defect, an intercostal muscle specimen was obtained at age 27 months. Immune deposits were absent from the endplates. On electron microscopy, most postsynaptic regions appeared normal, but the density of AChR on the junctional folds was diffusely reduced. In vitro microelectrode studies revealed that the number of transmitter quanta released by nerve impulse was normal. The amplitude of miniature of endplate potentials and currents was abnormally low. A study of the kinetic properties of AChR by analysis of acetylcholine-induced current noise demonstrated a significant decrease in mean channel open-time; the mean channel conductance was normal. The safety margin of neuromuscular transmission in this disorder is likely to be compromised by the deficiency and abnormal kinetic properties of AChR. The findings are unique among those patients with congenital AChR deficiency described to date.

Acetylcholinesterase↗
PubMed1993

Thymoma.

Thymomas and thymic carcinomas are thymic epithelial tumors that constitute approximately 15% of all mediastinal masses. From 28 to 66% of thymomas cause chest symptoms as the initial manifestation; the rest are discovered on routine chest roentgenograms or during investigations prompted by the presence of a paraneoplastic syndrome. Forty percent of patients with thymoma have one or more paraneoplastic syndromes, including myasthenia gravis, pure red cell aplasia, and hypogammaglobulinemia. Extrathymic malignant lesions develop in up to 20% of patients. Traditional histologic classifications have not accurately predicted tumor behavior; a recently developed classification based on cellular differentiation toward thymic medullary or cortical epithelium may correlate better with prognosis. Nevertheless, the prognosis is best predicted by stage of the tumor determined intraoperatively and is poorer in patients with incomplete resection than in those with complete resection of the thymoma. In addition to surgical intervention, irradiation and chemotherapy have important roles in the management of thymomas, particularly in advanced stages. In this article, the clinical manifestations, diagnosis, pathologic features, staging, and treatment of thymomas are reviewed, and the prognosis of affected patients is discussed.

Humans↗
PubMed1993

Congenital endplate acetylcholinesterase deficiency.

Endplate acetylcholinesterase (AChE) consists of globular catalytic subunits attached to the basal lamina by a collagen-like tail. Different genes encode the catalytic subunit and the tail portion of the enzyme. Endplate AChE deficiency was reported previously in a single case (Engel et al., 1977, patient 1). We describe here our observations in four additional patients (patients 2-5). Three cases were sporadic; patients 2 and 3 were sisters. All had generalized weakness increased by exertion but ophthalmoparesis was not a constant feature. All had mild slowing of the pupillary light reflex; other dysautonomic features were absent. None benefited from anticholinesterase therapy. All patients had a decremental electromyogram response; in four of the five patients, single nerve stimuli evoked a repetitive response. Miniature endplate potential amplitude was reduced in patient 5 only. Endplate amplitudes and currents were prolonged but the open-time of the acetylcholine receptor ion channel was normal. In patients 1-4 the quantal content of the endplate potential was reduced due to a reduced number of readily releasable quanta. Quantitative electron microscopy revealed abnormally small nerve terminals, abnormal encasement of the presynaptic membrane by Schwann cells and degeneration of junctional folds and of organelles in the junctional sarcoplasm. Acetylcholinesterase was absent from all endplates of all patients by cytochemical and immunocytochemical criteria. Density gradient ultracentrifugation of muscle extracts from patients 1, 3, 4 and 5 revealed an absence of the collagen-tailed form of the enzyme in patients 1, 3 and 4 but not in patient 5. The kinetic properties of the residual AChE in muscle were normal. Erythrocyte AChE activity and Km values, determined in three patients, were also normal. Studies of the catalytic subunit gene of AChE in patients 2 and 3 revealed no abnormality in those exons that encode the domain to which the tail subunit binds. In patients 1-4 the molecular defect is likely to reside in the gene encoding the tail subunit of AChE, or in a protein necessary to assemble the catalytic and tail subunits. In patient 5, the absence of AChE from the endplate may be due to a faulty tail subunit, a defect in the basal lamina site that binds the tail subunit or failure of transport of the assembled asymmetric enzyme from the cell interior to the basal lamina. The cause of the weakness in these patients is not fully understood but possible mechanisms are discussed.

Acetylcholinesterase↗
PubMed1992

Intraoperative electrophysiological monitoring in children.

Children, like adults, are at risk for neurological injury during a variety of surgical procedures. Intraoperative electrophysiological monitoring (IOM) provides information about the functional integrity of the nervous system during surgery. This information may determine the mechanism of injury and prevent damage by identifying nerves and detecting dysfunction at a reversible stage. Electrophysiological techniques may also help direct therapy by improving injury localization, detect the presence or absence of axonal integrity in peripheral nerve lesions, and identify rootlets with the greatest contribution to spasticity in patients undergoing selective dorsal rhizotomy (SDR). Electrophysiological techniques used are modified from those employed in the diagnostic laboratory. The first portion of this article reviews IOM experience at the Mayo Clinic in patients under 18 years of age from 1985 to 1991. The types of procedures monitored, the monitoring modalities used, technical problems unique to children, and neurological outcome are discussed. Subsequently presented are the application and techniques of electrophysiological monitoring during SDR as currently practiced at the University of Kentucky and other medical centers.

Brain Stem↗
PubMed1992

Effect of BAEP monitoring on hearing preservation during acoustic neuroma resection.

We measured the effect of brainstem auditory evoked potential (BAEP) monitoring on hearing preservation in acoustic neuroma resection in 90 consecutive patients with monitoring compared with 90 historical controls matched for tumor size and preoperative hearing status. In small tumors (less than 2 cm), BAEP monitoring was associated with a higher rate of hearing preservation and a greater chance that the hearing preserved was clinically useful. Changes in the BAEP intraoperatively showed a good correlation with postoperative hearing status.

Evoked Potentials, Auditory, Brain Stem↗
PubMed1992

Current results of the retrosigmoid approach to acoustic neurinoma.

Since 1984 when cranial nerve monitoring became routinely performed at the Mayo Clinic, 255 patients have undergone 256 procedures using the retrosigmoid approach for the removal of acoustic neurinomas. Of these, 221 patients had some hearing before surgery and 52 maintained hearing following surgery. The anatomical continuity of the facial nerve was preserved in 237 of these 256 procedures. It was possible to perform a primary end-to-end anastomosis in seven of the remaining 19 patients, and one patient had a cable graft inserted. Thus, 95.7% of these patients were believed to have potential for spontaneous facial nerve function. Of the 11 patients in whom this was not possible, seven underwent early spinal accessory facial anastomosis, in two hypoglossal-facial anastomosis was performed, and two had no facial nerve procedures and have paralysis of the facial nerve. There were two deaths from a pulmonary embolus in the early postoperative period, both 4 days following otherwise uneventful surgery. The most common postoperative complication was cerebrospinal fluid leakage, which has not resulted in significant permanent morbidity although early repair for this problem is now routinely recommended. Other complications were quite rare and have generally not resulted in any major change in patient lifestyle or activity level. This review reconfirms that the retrosigmoid surgical treatment of acoustic tumors continues to be an acceptable treatment option.

Adolescent↗
PubMed1992

Spinal cord injury in experimental thoracic aortic occlusion: investigation of combined methods of protection.

The efficacy of combined methods of spinal cord protection during thoracoabdominal aortic reconstruction was evaluated because a recent clinical study failed to substantiate the value of cerebrospinal fluid drainage when used alone in the prevention of paraplegia. The effect of cerebrospinal fluid drainage and aortofemoral shunting were analyzed with regard to neurologic outcome and spinal cord blood flow in a model of thoracic aortic occlusion. In addition, we studied the use of motor-evoked potentials as compared with somatosensory-evoked potentials in monitoring cord perfusion. Thirty-two dogs underwent proximal and distal thoracic aortic occlusion for 60 minutes. The control group (n = 8) underwent thoracic aortic cross-clamping only. Spinal cord protection was used in three groups: cerebrospinal fluid drainage alone (n = 8), aortofemoral shunting alone (n = 8), and cerebrospinal fluid drainage and aortofemoral shunting (n = 8). Neurologic outcome improved in all treatment groups as compared with controls (p less than 0.001). The addition of cerebrospinal fluid drainage to aortofemoral shunting did not further improve neurologic outcome. Spinal cord blood flow measured with microspheres in the lumbar gray matter was significantly higher in the dogs with aortofemoral shunting (+/- cerebrospinal fluid drainage) as compared with those with cerebrospinal fluid drainage alone (p less than 0.05) or the controls (p less than 0.001). Aortofemoral shunting also prevented the development of acidosis and hyperglycemia. Loss or changes in amplitude and latency of motor-evoked potentials did not distinguish between the groups. Loss of somatosensory-evoked potentials had a high sensitivity (92%) but lower specificity (68%) in predicting neurologic injury, whereas loss of motor-evoked potentials had a high specificity (100%) but a very low sensitivity (16%). We conclude that cerebrospinal fluid drainage or aortofemoral shunting significantly improve spinal cord blood flow and neurologic outcome. The greatest increase in spinal cord blood flow was seen with aortofemoral shunting, which also prevented metabolic disturbances of reperfusion. Although the addition of cerebrospinal fluid drainage to aortofemoral shunting was the only group in which no neurologic injury occurred, this group did not have a significant improvement in outcome when compared with aortofemoral shunting alone. Spinal cord ischemia was more accurately detected with somatosensory-evoked potentials when aortofemoral shunting was used, whereas motor-evoked potentials recorded from the spinal cord were not sensitive enough to predict neurologic injury.

Analysis of Variance↗
PubMed1991

Auditory monitoring during acoustic neuroma removal.

Preservation of hearing has become attainable for patients with small acoustic neuromas. Brain-stem auditory evoked response was monitored intraoperatively in 60 patients undergoing acoustic neuroma surgery via the posterior fossa approach. The overall rate of hearing preservation was 30% in the monitored group and 20% in 60 patients who were matched for tumor size and preoperative hearing level and underwent the same surgical procedure but without intraoperative brain-stem auditory evoked response monitoring. The rate of hearing preservation was correlated with tumor size: with tumors less than or equal to 1 cm, hearing was preserved in 82% of monitored and 36% of unmonitored patients; hearing was not preserved with tumors larger than 3 cm. Intraoperative brain-stem auditory evoked response monitoring appears to have improved the preservation of hearing during removal of small tumors.

Adolescent↗