Larry E. Davis

Cisplatin neuropathy. Clinical, electrophysiologic, morphologic, and toxicologic studies

Ten of 11 patients with ovarian cancer receiving cisplatin developed a distal sensory neuropathy, manifested early by decreased vibratory sensibility in toes and depressed ankle jerks and later by uncomfortable paresthesias. Eleven patients receiving cisplatin, 50 mg/m2 monthly (mean total, 580 mg/m2) were studied prospectively with monthly neurologic examinations and conduction velocity determinations of median, peroneal, and sural nerves. Early signs were decreased vibratory sensibility in toes (mean dose, 417 ± 132 mg/m2 [SD]) and loss of ankle jerks (mean dose, 455 ± 86 mg/m2). With continued therapy, four developed paresthesias. Strength was unaffected. Sural nerve responses abruptly disappeared in six patients (mean dose, 383 ± 103 mg/m2). Other conduction velocities remained normal. Electron microscopy of peripheral nerves from four patients showed axonal degeneration and secondary myelin breakdown. Platinum concentrations in three patients were similar in tumor (3.3 μg/g), sural nerves (3.5 μg/g), and spinal ganglia (3.8 μg/g), but lower in brain (0.17 μg/g). This may explain the cisplatin toxicity of peripheral nerves with relative sparing of the central nervous system.

Intralabyrinthine Osteogenesis in Cogans's Syndrome

Temporal bones from a 64-year-old man who had Cogans syndrome were examined by light microscopy. Although tissues of the middle ear appeared unremarkable, extensive ectopic bone formation was observed bilaterally in the inner ear membranous labyrinth. Such osteogenesis completely obliterated the cochlear compartments apically. Only the scala tympani compartment of the basal cochlear turn remained patent. Ectopic bone tissue was observed also in the vestibular semicircular canals. Marked degeneration of eighth nerve fibers and associated ganglion cells also was observed, To our knowledge, this report represents only the fourth temporal bone findings of Cogans syndrome and demonstrates a more advanced pathologic state of inner ear pathology than those reported previously.

HIV-1 infection despite immediate combination antiviral therapy after infusion of contaminated white cells

We present a sixth human case in which primary human immunodeficiency virus (HIV-1) infection occurred, despite antiretroviral prophylaxis, after accidental inoculation of infected blood. In the prior five instances, variables such as large virus dose, late administration of antivirals, viral resistance to zidovudine, and pre-existent immunosuppression, may have played a role in the treatment failure. In this case, high-dosage oral zidovudine was given within minutes of the accident and replaced 2 1/2 days later with interferon alpha and dideoxyinosine (ddl). Despite aggressive treatment, HIV-1 infection was demonstrated in blood, spleen, and brain tissue at autopsy 16 days later. Of the tissues studied, detection of HIV-1 was most prominent in the spleen. Double-label immunocytochemistry confirmed the morphologic impression that while some of the infected spleen cells were CD3-positive T cells, the majority were macrophages. Thus, current single or dual (zidovudine, ddl-interferon) therapies for accidental HIV-1 inoculation may not be effective in preventing early infection. Further trials in animals appear warranted to evaluate protection by other strategies, such as passive immunity or combinations of agents that penetrate the brain and attack HIV-1 viral replication at differing sites.

Cytomegalovirus isolation from a human inner ear.

Cytomegalovirus (CMV) infection of the fetus has been associated with congenital deafness or hearing loss. This association has previously been based on clinical or pathological studies. We report an infant who died with the congenital CMV syndrome in which CMV was isolated from the perilymph of the inner ear providing additional evidence that this virus can infect the labyrinth.

Somatosensory evoked magnetic fields in patients with stroke

We used magnetoencephalography to evaluate areas of sensory cortex in patients with ischemic strokes involving the somatomotor system. We measured somatosensory evoked magnetic fields using a 7-channel neuromagnetometer and estimated the location of cortical responses to median nerve stimulation in 5 patients with cortical or subcortical strokes involving the somatomotor system. All patients underwent quantitative neurological examinations and a high resolution volumetric magnetic resonance imaging. The estimated current dipoles were localized onto the patients own MRI scan in all patients with measurable responses. The location of the estimated dipole was always in non-infarcted tissue in the anatomical region of the somatosensory cortex. In 1 patient the somatosensory dipole localized to a peninsula of cortex flanked by infarcted tissue. Single photon emission computed tomography found the localized area of cortex to have significant blood flow. The estimated current dipole strengths of somatosensory evoked fields from median nerve stimulation correlated significantly (r = 0.95, P < 0.02) with the patients ability to recognize numbers written on the involved palm (graphesthesia). The combination of evoked magnetic field recording and magnetic resonance imaging is a promising non-invasive technology for studying brain function in patients with cerebrovascular disease.

Pre-mortem diagnosis of Creutzfeldt-Jakob disease by detection of abnormal cerebrospinal fluid proteins

Creutzfeldt-Jakob disease (CJD) may be difficult to diagnose early or when it has an atypical presentation. We describe two patients with progressive dementia in whom the results of diagnostic brain biopsies were unhelpful. Spinal fluid from these patients, analyzed by two-dimensional electrophoresis, contained two abnormal proteins (Nos. 130 and 131, with relative molecular masses of 26,000 and 29,000 daltons and isoelectric points of 5.2 and 5.1). These findings suggested a provisional diagnosis of Creutzfeldt-Jakob disease, which was confirmed in both patients at autopsy. Detection of these abnormal cerebrospinal fluid proteins appears to be a valuable laboratory adjunct in evaluating patients with an unexplained progressive dementia.

The influenza B virus mouse model of Reye's syndrome: clinical, virologic and morphologic studies of the encephalopathy

The influenza B virus mouse model of Reyes syndrome was studied to learn more about the encephalopathy in Reyes syndrome. One to 3 days after intravenous influenza B/Lee virus, Balb/c mice became lethargic, seized and lapsed into a fatal coma. Wide-spread cerebral edema without inflammation developed 1-3 days after virus inoculation. Swollen astrocytic foot processes containing increased glial fibrillary acidic protein were located around capillaries. Viral particles were not seen by electron microscopy and complete viral replication did not occur. Immunohistochemical studies demonstrated influenza B viral antigen within many endothelial cells but not within other brain cells. Qualitative (Evans blue dye) and quantitative (percent brain water and technetium -99 pertechnetate) studies of the blood-brain barrier demonstrated abnormalities. This model reproduced many clinical, virologic and pathologic features of the Reyes syndrome encephalopathy. In addition, a non-permissive viral infection of brain endothelial cells occurred which may be important in the pathogenesis of the mouse encephalopathy and may participate in the encephalopathy of Reyes syndrome.

Causes of Death of Patients in an Institution for the Developmentally Disabled

The causes of death of 53 severely to profoundly developmentally disabled patients who died in an intermediate care facility were reviewed. Respiratory disease, predominantly pneumonia and aspiration, accounted for 72% of deaths. Seven patients died of nonrespiratory causes, and in 8 patients, no cause of death could be determined, even after a complete autopsy or investigation. The median age at death was 20 years. The weights of these patients organs at autopsy were lower than those for normal individuals of the same age. The lifespan of these severely impaired individuals continues to be significantly shortened, even with improved methods of care.

The Sequence of Changes in Liver and Brain in the Influenza B Virus Mouse Model of Reye's Syndrome

The time course of morphologic changes in the influenza B mouse model of Reyes syndrome is described and compared to the clinical, virologic, and biochemical changes. Following an intravenous inoculation of a lethal dose of an egg adapted strain of influenza B/Lee/40 virus, mice first showed clinical signs of lethargy and ruffled fur at 12 hours (h) post inoculation (pi). The earliest morphologic changes in the liver occurred at 12 h pi, and consisted of a slight increase in fat and loss of glycogen in hepatocytes. Over the next 36 h, the accumulation of micro vesicular fat increased, and mitochondrial abnormalities such as pleomorphism and loss of dense bodies developed. There was no increase in peroxisomes. In the brain, focal cerebral edema was detected as early at 6—12 h pi. The edema, manifested as swelling of astrocytic foot processes, increased in severity with time. Endothelial cells were not abnormal. Myelin sheath splitting rarely was observed. Since changes occurred simultaneously in the liver and in the brain, we suggest that influenza B virus caused a simultaneous primary insult to both organs.

Natural history of frequent recurrences of herpes simplex labialis

We prospectively studied all herpes simplex labialis (HSL) episodes in a group of 84 (age, 6 to 71 years) persons who previously had frequent recurrences of HSL to determine whether their recurrences of HSL were different from those of the general population. The mean +/- standard error for number of HSL outbreaks for 6 months was 2.7 +/- 0.3. Age, gender, or season did not influence the recurrence rate. The mean time to vesicle healing of 214 outbreaks was 6.4 +/- 0.2 days. Again, age or gender did not influence healing time. An episode of HSL did not elicit a refractory period to the next attack of HSL. Furthermore, the severity of the previous HSL lesion did not influence the interval to next recurrence or the location of the next lesion. In 47%, the next recurrence of HSL crossed the midline of the face, and in 45%, it moved from one lip to the other. The high recurrence frequency and multiple facial locations of HSL lesions seen in these persons differed from the general population, who report infrequent lesions of HSL at the same facial location.