Slower Functional Recovery Research Articles

Regeneration after tall hair cell damage following severe acoustic trauma in adult pigeons: correlation between cochlear morphology, compound action potential responses and single fiber properties in single animals

The time course of recovery of compound action potential (CAP) thresholds was observed in individual adult pigeons after severe acoustic trauma. Pigeons were overstimulated with a tone of 0.7 kHz and 136–142 dB SPL presented to one ear for 1 h under general anesthesia. Recovery of CAP audiograms was monitored at regular intervals after trauma. A new semi-stereotaxic approach to the peripheral part of the auditory nerve was developed. This permitted activity from single auditory nerve fibers to be recorded over a wide range of characteristic frequencies (CFs), including high CFs, without having to open the inner ear. Single unit recordings were made after three weeks and after 4 or more months of recovery. The time course of recovery, the single unit properties, and the morphological status of the basilar papilla were correlated. The CAP was abolished in all animals after overstimulation. Three groups of animals were identified according to the functional recovery of the CAP thresholds recorded at regular intervals with implanted electrodes: Group 1: Fast functional recovery starting immediately after trauma, followed by recovery to pre-exposure values within 3 weeks. Group 2: Slow functional recovery of threshold starting 1–2 weeks after trauma and ending 4–5 weeks after trauma. A mean residual hearing loss of 26.3 dB at 2 kHz remained. Group 3: No recovery of CAP thresholds up to 8 months after trauma. Three weeks after trauma, very few responsive neurons were found in groups 2 and 3. Tuning curves were very broad and sometimes irregular in shape. Thresholds were very high, around 120 dB SPL. Spontaneous firing rate was much reduced, especially in neurons with high CFs. After 4 or more months of recovery, the response properties of single units in group 1 had only partially recovered. Thresholds and sharpness of tuning of many single units were normal; however, in general they were still poorer than in control animals. Spontaneous firing rate was comparable to control animals. Neurons from animals in group 2 showed less recovery, especially at frequencies above the exposure frequency. Thresholds and sharpness of tuning were normal at frequencies below the exposure frequency, but were much poorer at frequencies above the exposure. Spontaneous firing rate was much reduced in fibers with high CFs. The basilar papilla in animals without recovery showed total loss of the sensory epithelium. The basal lamina of the basilar membrane, however, remained intact and was covered with cuboidal cells. In fast recovering animals, the papilla was repopulated with hair cells after 4 months. In slow recovering animals, short (abneural) hair cells were still missing over large parts of the papilla after 4 months of recovery. Residual short (abneural) hair cell loss was largest at two areas, one more basal and the other more apical to the characteristic place of the traumatizing frequency. The results show that functional recovery from severe damage to both short (abneural) and tall (neural) hair cells occurs in adult birds. However, the onset of recovery is delayed and the time course is slower than after destruction of short (abneural) hair cells alone. Furthermore recovery is incomplete, both functionally and morphologically. There are residual permanent hearing losses and regeneration of short (abneural) hair cells is incomplete.

Long-term Effects of Chronic Otitis Media on Binaural Hearing in Children

To determine the long-term effect of otitis media with effusion (OME) on binaural hearing in children. Longitudinal testing over a 4-year period following insertion of tympanic membrane grommets, employing clinical and normal control groups. Twenty-two children with a history of OME were tested before insertion of grommets and at 3 months and 1 year after surgery; 14, 11, and 8 of the children were followed up for 2, 3, and 4 years after surgery, respectively. An age-matched control group of 40 children was tested. The masking-level difference (MLD) paradigm was used to measure the ability of the binaural auditory system to aid the detection of a pure-tone signal presented in a random masking noise. Although the results indicated a significant improvement in the MLD with increasing time after middle ear surgery, the MLD remained significantly reduced even 2 years after hearing threshold correction. The MLDs of the OME group did not differ significantly from those of the control group when tested 3 years after middle ear surgery, even though a small proportion of subjects with a history of OME continued to have MLDs smaller than normal limits. In general, the results suggest a slow recovery of binaural function in children with OME after restoration of normal hearing thresholds.

Specific antibodies against the Zn(2+)-binding domain of clostridial neurotoxins restore exocytosis in chromaffin cells treated with tetanus or botulinum A neurotoxin.

Although tetanus and botulinum A neurotoxins are ineffective in cultured chromaffin cells, they will inhibit carbachol-induced release of noradrenaline provided they gain access to the cytosol either through artificial pores generated in the plasma membrane or by binding to incorporated exogenous gangliosides. The block of exocytosis persists for weeks followed by a slow recovery of cell function. When specific anti-botulinum A toxin antibodies are introduced into cells through pores after manifestation of the block by botulinum A neurotoxin, restoration of exocytotic function is accelerated and fully reestablished within 4 days. The same time course of restoration is seen with anti-tetanus toxin antibodies in cells poisoned by tetanus toxin. Since the light chains of the toxins are enzymatically active, we have introduced polyclonal and monoclonal anti-light chain antibodies into the cytosol. Of all light chain antibodies tested, only those directed against the peptide homologous to the zinc-binding sequence, which is present in both neurotoxins, restored exocytosis regardless of which toxin caused the block. These results indicate that the zinc-binding domain is directly involved in the interaction of the light chains with their substrates and that the toxins have to be present continuously to maintain the block.

Concurrent Presentation of Hemolytic Uremic Syndrome in Two Adult Siblings: Effects of Plasma Therapy on Hemolysis and Renal Function

We describe 2 sisters who presented with the hemolytic uremic syndrome (HUS) almost simultaneously. In both patients an upper airway infection with Haemophilus influenzae immediately preceding HUS may have been the environmental trigger. Fresh plasma infusion had only minor therapeutic effects but plasma exchange was followed by hematological remissions. One patient stayed dialysis dependent, the other had slow recovery of renal function on prolonged plasma exchange. These case histories suggest that in genetically predisposed patients HUS can be triggered by an infection with H. influenzae. Furthermore, when there is a poor response to plasma infusion recovery may be accelerated by plasma exchange.

Efficacy of long-term therapy with low doses of omeprazole in the control of gastric acid secretion in Zollinger-Ellison syndrome patients.

Thirteen patients with Zollinger-Ellison syndrome were investigated: 8 without, and 5 with, previous gastric surgery. After 7-34 months of treatment with famotidine, 8 out of 13 patients were resistant to this drug. Omeprazole 60 mg/day was administered to these 8 patients; after one month, the dose was reduced to 40 mg/day, and after another month to 20 mg/day. Basal acid secretion was inhibited by every dose of omeprazole. The patients were then treated with a low dose (20 mg/day) of omeprazole for a longer period. Periodic clinical and endoscopic assessments, and measurement of basal acid secretion showed the efficacy of this low dose of omeprazole in our Zollinger-Ellison syndrome patients. The drug was discontinued after 12-32 months of omeprazole treatment, and gastric acid recovery was evaluated. Four patients recovered 50% of their 'initial basal acid secretion' after 5 days, while two patients who had been treated with omeprazole for a longer time (30-32 months) recovered only 38 and 40%, respectively, of their 'initial basal acid secretion' at the tenth day. Our results indicate that the omeprazole dosage to be used in the treatment of Zollinger-Ellison syndrome must be chosen principally on the basis of basal acid secretion determination. A low daily dose of omeprazole is able to control acid secretion in Zollinger-Ellison syndrome for a long period (10-30 months). The slow recovery of gastric secretory function demonstrates the prolonged inhibitory effects of omeprazole.

Auditory and neuropsychiatric behavior patterns after electrical injury.

Major electrical injury causes widespread tissue destruction. Slow and incomplete functional recovery after electrocution-type injury has led clinicians to suspect residual brain damage. One hundred and one consecutive patients who were admitted to the hospital because of electrical injury were studied. Forty-eight had electric-current injury. The other 53 had flash, contact, or arcing burns (electrical injury without passage of current). A primary study cohort of 16 patients with electric-current injury and 18 patients who had electrical injury without passage of current received specialized trauma-based psychiatric treatment, which was coordinated with serial auditory and neurologic studies. This strategy served to highlight discrepancies between preinjury and postinjury performance. Twelve of 16 patients with electric-current injury showed neurobehavioral (organic) dysfunction after 1 year, which implied brain damage; eight showed persistent auditory changes. Four of 18 patients who had electrical injury without passage of current met criteria for post-traumatic stress disorder after 1 year; none had neurobehavioral or auditory dysfunction. These findings indicate that patients with electric-current injury are at risk for permanent auditory dysfunction and brain damage, whereas those with other types of electrical burns are not.

Reinstatement of motor deficits in recovered brain-injured animals: the role of cerebellar norepinephrine

Previous research has indicated that antagonists of locus ceruleus functioning, when administered during the acute phase of an injury, slow recovery of motor function following unilateral sensorimotor cortex injury. Following a recovery plateau in animals, it is possible to pharmacologically reinstate unilateral motor deficits in recovered animals with similar acting drugs given intraperitoneally. The present study was designed to localize the brain systems responsible for the reinstatement of the deficit after recovery from the cortical injury. The results indicate that maintaining functional recovery after injury is modulated by NE in the cerebellum contralateral to the injury, since microinfusions of phenoxybenzamine into this structure reinstate motor deficits. Additionally, removal of the noradrenergic projection to contralateral cerebellum through unilateral lesions of the locus ceruleus reinstate unilateral deficits more severely than the drug administration.

Slow and incomplete histological and functional recovery in adult gluten sensitive enteropathy.

To assess the course of recovery of gluten sensitive enteropathy in adults, histological and functional recovery was studied in 22 patients, aged 20-79 years. Biopsy specimens taken at the time of diagnosis were studied in 20; after adhering to a gluten free diet for nine to 19 (mean 14) months in 14; and after adhering to the same diet for 24-48 (mean 34) months in 10 patients. Histological recovery was assessed morphometrically in the proximal jejunum. Mucosal linings significantly improved over time, but did not completely return to normal with a gluten free diet: at diagnosis the surface: volume ratio was 22% of normal, increasing to 48% and 66% after nine to 19 and 24-48 months, respectively, of a gluten free diet. Disaccharidase activities progressively increased. After 24-48 months maltase, sucrase, and isomaltase had returned to normal in the proximal jejunum; they were still significantly decreased in the distal duodenum. Duodenal and jejunal lactase activities were both below normal after 24 to 48 months. It is concluded that recovery of the intestinal mucosa of adults with gluten sensitive enteropathy during a gluten free diet continues beyond nine to 19 months and is still incomplete after two to four years. The recovery of disaccharidase activities extends from the distal to the proximal part of the small intestine, and is aligned to histological recovery.

Recovery of respiration after neuromuscular blockade with alcuronium.

Alcuronium 0.2 mg kg-1 was given to six patients to investigate the simultaneous recovery of breathing and peripheral neuromuscular function. Anaesthesia was maintained with 66% nitrous oxide in oxygen supplemented with 0.5% halothane, and the patients were ventilated to normocarbia. Patients were disconnected from the ventilator after the reappearance of the tetanic response. This response returned at a mean time of 19.2 min after the injection of alcuronium and oxygenation was maintained thereafter by means of apnoeic diffusion. Spontaneous breathing returned at a mean time of 23.6 min after the injection of alcuronium. Sixty minutes after the administration of alcuronium, respiratory exchange was judged adequate, and at that time neuromuscular function was still markedly depressed with a tetanic height less than 25% of control. It was concluded that, because of the slow recovery of neuromuscular function, alcuronium should be reserved for the longer surgical procedure.

Trimethyltin exposure produces an unusual form of toxic auditory damage in rats

A single injection of trimethyltin chloride (TMT; 2, 4, or 6 mg/kg) is shown to produce a frequency-specific, dose-dependent auditory impairment, as well as to decrease the amplitude of the acoustically elicited startle response, in exposed rats. This finding stands in contrast to data presented earlier on the effects of triethyltin bromide (TET), which produces changes in startle response without affecting auditory acuity. Animals intoxicated with TMT at moderate doses appear to recover their auditory acuity over the course of several weeks. This slow recovery of auditory function, which is uncharacteristic for chemical ototoxicity, suggests that TMT may be a useful model agent for studying ototoxic mechanisms.

Sustained regional abnormalities in cardiac metabolism after transient ischemia in the chronic dog model

Positron emission tomography allows noninvasive assessment of myocardial blood flow and metabolism, and may aid in defining the extent and severity of an ischemic injury. This hypothesis was tested by studying, in chronically instrumented dogs, regional blood flow and metabolism during and after a 3 hour balloon occlusion of the left anterior descending coronary artery. The metabolic findings after ischemia were compared with the recovery of regional function over a 4 week period. N-13 ammonia was used as a blood flow tracer, and C-11 palmitic acid and F-18 deoxyglucose as tracers of fatty acid and glucose metabolism, respectively. Regional myocardial function was monitored with ultrasonic crystals implanted subendocardially. Regional function improved most between 24 hours and 1 week after reperfusion, but was still attenuated at 4 weeks. The slow functional recovery was paralleled by sustained metabolic abnormalities, reflected by segmentally delayed clearance of C-11 activity from myocardium and increased uptake of F-18 deoxyglucose. Absence of blood flow and C-11 palmitic acid uptake at 24 hours of reperfusion correlated with extensive necrosis as evidenced by histologic examination. Conversely, uptake of C-11 palmitic acid with delayed C-11 clearance and increased F-18 deoxyglucose accumulation identified reversibly injured tissue that subsequently recovered functionally and revealed little necrosis. Thus, recovery of metabolism after 3 hours of ischemia is slow in canine myocardium and paralleled by slow recovery of function. Metabolic indexes by positron tomography early after reperfusion can identify necrotic and reversibly injured tissue. Positron tomography may therefore aid in defining the extent and prognosis of an ischemic injury in patients undergoing reperfusion during evolving myocardial infarction.

Strictures and other late complications of neonatal necrotising enterocolitis

Eighty infants have been treated for neonatal necrotising enterocolitis within a period of five years. Twenty-five per cent developed strictures of the small or large intestine. Four cases of atresia including two with multiple cyst formation were seen. Four patients developed severe malabsorption requiring hyperalimentation with slow recovery of small bowel function in two survivors. The radiological features of these complications is illustrated and the role of radiology in the management of these patients is discussed.

Cerebrospinal fluid acidosis complicating therapy of experimental cardiopulmonary arrest.

Cardiopulmonary resuscitation (CPR) may be followed by slow recovery of brain function. The possible role of bicarbonate therapy was assessed by analysis of arterial blood and cerebrospinal fluid (CSF) in 20 dogs during cardiac arrest and CPR. Samples were taken in the control period and every 5 minutes post-arrest of 20 minutes. Group I received no post-arrest CPR. Arterial pH fell from 7.37 to 7.31 (P less than 0.01) and CSF pH from 7.34 to 6.94 (P less than 0.001). Arterial pCO2 rose from 39 to 65 mm Hg (P less than 0.005) and CSF pCO2 increased from 47 to 123 (P less than 0.02). With CPR alone (group II) arterial pH decreased from 7.39 to 7.19 (P less than 0.005), while arterial pCO2 and CSF pH and pCO2 were undhanged. CPR with bicarbonate therapy (mEq = weight in kg times 0.43 times 1.1 mEq/min of arrest) given every 5 minutes (group III), resulted in a rise in arterial pH from 7.41 to 7.81 (P less than 0.02). Excess bicarbonate administration during CPR may result in a marked dissociation between arterial and CSF pH as a consequence of rapid CO2 diffusion across the blood-brain barrier. Large ampounts of NaHCO3 given during CPR may contribute to post-CPR cerebral depresssion.