An atypical case of Trypanosoma cruzi infection in a young English Mastiff.

A case of Trypanosoma cruzi infection in a young English Mastiff from Texas is presented. Clinical signs and laboratory findings included subcutaneous edema, lymphadenopathy, weight loss, and hypoalbuminemia. Cytology of a lymph node revealed numerous amastigotes. No trypomastigotes were observed in buffy coat preparation of peripheral blood, and on histologic evaluation, most organs contained numerous interstitial pseudocysts. Initial serology was positive for both T. cruzi and Leishmania, and immunohistochemistry supported a diagnosis of Leishmania. However, additional serology supported a T. cruzi infection, and cultivation of organisms isolated from a lymph node revealed morphology consistent with T. cruzi. In addition, PCR analysis resulted in a 504 bp fragment with 99% homology to a flagellar protein of T. cruzi. Although uncommon, autochthonous cases of both T. cruzi and Leishmania have been reported in the United States. Clinical signs observed with both diseases can show many similarities, cytology may be indistinguishable, as in this case, and serological cross-reactivity is common. This case demonstrates an unusual presentation of T. cruzi and the use of multiple testing strategies to support its diagnosis.

The application of F-wave measurements in the differentiation of proximal and distal upper limb entrapments.

Conduction velocities of the proximal segments of the median and ulnar nerves were measured by evoking F-wave responses. The results of these and conventional motor and sensory studies from 60 control subjects were compared with the results in 30 patients with carpal tunnel syndromes, 18 patients with cubital tunnel syndromes, and 23 patients with suspected proximal entrapments. Sixty-seven percent of patients with proximal lesions (confirmed by myelography in 60 percent of cases) had abnormalities in their F-wave studies. Conventional motor studies were normal. Twenty-three percent of the patients with carpal tunnel syndrome and 11 percent of the patients with cubital tunnel syndrome also had abnormal F-wave studies, indicating an additional element of proximal entrapment. This technique is felt bo be useful in differentiating between distal and proximal entrapments.

Evaluation of heme oxygenase-1 as a systemic biological marker of sporadic AD.

BACKGROUND: Heme oxygenase-1 (HO-1) is a 32-kDa stress protein that catalyzes the degradation of heme to biliverdin. HO-1 immunoreactivity is greatly increased in neurons and astrocytes of the hippocampus and cerebral cortex of individuals with AD and colocalizes to senile plaques and neurofibrillary tangles. METHODS: We investigated whether systemic HO-1 regulation is also deranged in AD patients and whether blood HO-1 measurements provide a peripheral biomarker of the disease. Plasma HO-1 protein levels were measured by competitive ELISA and lymphocyte HO-1 mRNA levels were determined by Northern analysis in patients with early probable sporadic AD, normal elderly controls (NEC), normal younger controls, individuals with age-associated cognitive decline (AACD) not meeting AD criteria, and patients with non-Alzheimer dementia, nondementing neurologic illness, and chronic medical disorders. CSF HO-1 protein concentrations were also determined by ELISA in pathologically confirmed AD and control cases. RESULTS: Mean plasma HO-1 protein concentrations were significantly lower in AD patients (0.85 +/- 0.14 microg/mL) compared with NEC (1.77 +/- 0.34 microg/mL; p < 0.05) and control patients. The AACD group exhibited plasma HO-1 concentrations (1.06 +/- 0.33 microg/mL) intermediate between, but not different from, those of the AD patients and NEC. Lymphocyte HO-1 mRNA levels were lower in the AD cohort relative to NEC (p < 0.001) and individuals with AACD, non-Alzheimer dementia, nondementing neurologic illness, and chronic medical conditions. Lymphocyte HO-1 mRNA levels were also lower in the AACD group relative to NEC (p < 0.05). In comparison with all groups excluding AACD, the sensitivity and specificity of lymphocyte HO-1 mRNA measurement for diagnosis of early sporadic AD are 88% and 75%. Mean CSF HO-1 protein concentrations were lower (p < 0.01) in AD cases (19.07 ng/mL) relative to control values (32.48 ng/mL). CONCLUSIONS: Plasma and CSF HO-1 protein and lymphocyte HO-1 mRNA levels are decreased in subjects with sporadic AD. Quantitative assay for lymphocyte HO-1 mRNA expression may serve as a useful biologic marker in early sporadic AD.

Peripheral neuropathy with IgM kappa monoclonal immunoglobulin directed against myelin-associated glycoprotein.

Three patients with a monoclonal IgM kappa paraproteinemia had a slowly progressive segmental demyelinating peripheral neuropathy. Sural nerve biopsies showed predominantly large fiber loss, with widening of the intraperiod line of myelin associated with active demyelination. Immunoblot analysis showed reactivity of IgM to myelin-associated glycoprotein (MAG) of human myelin. An enzyme-linked immunosorbent assay (ELISA) was developed to provide a simple quantitative technique for detection of antibodies to MAG. Treatment with corticosteroids, immunosuppressive agents, and plasmapheresis produced no significant improvement.

Progressive myoclonus epilepsy in young adults with neuropathologic features of Alzheimer's disease.

Progressive myoclonus epilepsy (PME) may develop in adult life. We present two patients with PME appearing around the age of 30 years in whom the disorder represented a manifestation of Alzheimer's disease. This diagnosis must be considered in addition to possible Kufs' disease or myoclonic epilepsy with ragged red fibers (MERRF) when PME develops in young adults.

Experimental mitochondrial myopathy produced by in vivo uncoupling of oxidative phosphorylation.

Two uncouplers of mitochondrial oxidative phosphorylation [2,4-dinitrophenol (DNP) and carbonylcyanide-m-chlorophenylhydrazone (CCCH)] were infused intra-arterially into a branch of the lower abdominal aorta of anesthetized rats over a 60-180 min period. An acute, severe, hypermetabolic state with systemic lactic acidosis and stiffness of the lower extremeities developed. In the plantaris muscles, by histochemistry, numerous "ragged red" fibers were present after the infusion. The "ragged red" areas presumably represented an absolute increase in mitochondrial mass in affected muscle fibers. By electron microscopy, linear inclusions were present in the intracristal space of many mitochondria. Simultaneous infusion of DNP and chloramphenicol, an inhibitor of mitochondrial protein synthesis, prevented the formation of ragged red fibers but not the intracristal inclusions. Infusion of relatively large amounts of oleic acid produced histochemical and electron-microscopic changes similar to those caused by the uncouplers. A possible pathogenesis of these reversible mitochondrial changes was discussed and their potential relevance to morphologic abnormalities of skeletal muscle mitochondria in human diseases was reviewed.

An electrophysiological method for examining lumbosacral root compression.

The propagation velocities and conduction times of nerve impulses responsible for muscle F-waves were measured in the proximal segments of 60 normal posterior tibial nerves and of 41 normal peroneal nerves. The results were compared with those of 25 patients having confirmed lumbosacral root compression due to disc degeneration. Using the peroneal nerve, 65 per cent of patients had a prolonged proximal conduction time; a similar abnormality was found in 56 per cent of patients when the posterior tibial nerve was studied. The yield of positive results rose to 85 per cent and 76 per cent respectively when the M- and F-latencies in given individuals were compared. It was also shown that in normal subjects the F-response has a longer latency, and slower conduction velocity than the H-reflex when both are obtained using the same stimulating and recording sites. In patients in whom the ankle jerks and H-reflexes are absent, the F-waves may still be recorded indicating that the latter are mediated through motor fibers.

Sensorineural deafness in early acquired syphilis.

A 36 year old male developed bilateral sensorineural deafness as the chief manifestation of secondary syphilis. Cerebrospinal fluid showed pleocytosis. Treatment with penicillin and prednisone resulted in good recovery of hearing. Initial recovery seemed dependent on corticosteroids. Deafness can complicate acquired syphilis in both early and late stages of the disease and may be its sole manifestation. Early acquired syphilitic deafness is usually the result of a meningitis affecting the eighth nerve and responds well to treatment. These features are contrasted with those of late acquired syphilitic deafness.

Anoxic tonic seizures due to asthma; a serious complication in adults.

Anoxic tonic seizures are reported as a complication of severe asthma in two adults. The nature of these attacks can be misinterpreted. They do not indicate the presence of a recurrent seizure problem unconnected to the episodes of anoxia caused by asthma. These attacks do not respond to antiepileptic medication, but cease if the asthma can be controlled. One of our patients developed an anoxic encephalopathy and the other died. The need for prompt diagnosis and appropriate treatment is emphasized.

Prolonged delirium without anticholinergic signs following amitriptyline overdose.

In a case of acute intoxication with a tricyclic antidepressant (amitriptyline) delirium was prolonged without there being prominent peripheral anticholinergic or electrocardiographic signs. Administration of physostigmine, repeated when necessary, reversed the delirium.

Cylindrical spirals in human skeletal muscle.

Muscle biopsies from two patients revealed that numerous type 2 fibers contained large abnormal areas filled with cylindrical spirals. The cytochemical profile of these cylindrical spirals was sufficiently characteristic that they could be distinguished from tubular aggregates. Their electron microscopic appearance was unmistakable. Their origin and significance are uncertain. The diverse nature of the patients' conditions (cramps and malignancy, and an unusual form of spinocerebellar degeneration) indicate that these abnormal structures are not disease specific.

Symmetry and synkinesis during rehabilitation of unilateral facial paralysis.

We evaluated biofeedback rehabilitation in patients with severe chronic unilateral facial paralysis, who had intact facial-motor innervation (House grades 3 to 5). Recovery of facial function was characterized (1) by grading facial movement symmetry, and (2) by counting the number of muscles exhibiting synkinesis during maximal execution of selected facial movements (e.g., smiling). Facial function in 21 patients typically improved by one House grade. Facial symmetry recovered rapidly during the first 5 months of treatment, and then improved more slowly. However, during this latter period, examination of the relationship between symmetry and synkinesis (visualized by a graph plotting symmetry grades on the x-axis, against the number of synkinetic muscles on the y-axis) indicated that overall facial control was improving even when House grading suggested that it was not. Such information should aid facial retraining and may clarify understanding of underlying rehabilitation mechanisms.

Mitochondrial dysfunction in multiple symmetrical lipomatosis.

Multiple symmetrical lipomatosis is a striking clinical finding associated with a variety of peripheral and central nervous system abnormalities. We describe 4 unrelated patients with evidence of mitochondrial dysfunction in skeletal muscle. Multiple symmetrical lipomatosis is an additional, albeit unusual, manifestation of the expanding clinical spectrum of mitochondrial diseases.