Should Delayed Cholecystectomy Following Acute Calculous Cholecystitis Be Discouraged in a Resource-restricted Setting?

BACKGROUND: Early cholecystectomy for acute calculous cholecystitis (ACC) reduces hospital stay and complications during the waiting period. The purpose of this study is to establish the patterns of management of ACC at the University Hospital of the West Indies (UHWI) and to evaluate the advantages of early versus delayed cholecystectomy. METHODS: This was a retrospective chart review of patients admitted with a diagnosis of ACC. Data collection included demographics, management strategy, timing to cholecystectomy, significant events while awaiting cholecystectomy and duration of hospital stay. Mann-Whitney U and Chi-squared tests were used for analysis. P-value of < 0.05 was considered significant. RESULTS: A total of 102 patient charts were extracted, 59 of which were managed conservatively and 43 managed with early cholecystectomy. The mean time to surgery after conservative management was 173 days. About 30% of persons managed conservatively had significant attacks while awaiting surgery, which included need for re-admission and earlier intervention. There was a trend toward longer mean total hospital stay in the conservative group (xsx = 5.03, xCons = 6.12; p = 0.054). CONCLUSION: Conservative management of ACC results in significant delays in definitive management and risks of complications during the waiting period. Early cholecystectomy should be encouraged even in a resource-restricted setting.

The Impact of Trans-thoracic Ultrasound on Cardiac Injuries.

OBJECTIVE: To determine the impact of trans-thoracic ultrasound (TTUS) in patients with chest trauma and potential cardiac injuries and to determine the outcome of patients with cardiac injury detected on TTUS. METHOD: Data were obtained from the Trauma Registry for all patients presenting alive to the University Hospital of the West Indies during the 10-year period commencing January 1, 2001 and who were subjected to a TTUS or emergency thoracotomy for cardiac injuries, or had cardiac injuries at postmortem. In addition to demographics, variables analysed included mechanism and site of injury and outcome. RESULTS: Of 405 patients being subjected to a TTUS during the period, 12 (3%) had cardiac injuries. During the same period, 63 patients in the Trauma Registry had proven cardiac injuries. Trans-thoracic ultrasound was thus conducted on 19% of all patients with cardiac injuries. Three patients had positive TTUS but no cardiac injuries. Of the patients with injuries, the mean age was 30.4 years, 92.1% were male and 65% were as a result of stab wounds, while 22% were as a result of gunshot wounds. The right ventricle was the most common site of injury, accounting for 41% of cases, while the left ventricle, both ventricles and other sites accounted for 27%, 17% and 14%, respectively. Ninety per cent of the group was subjected to emergency thoracotomy; mortality of the entire group was 48%, including one patient who had TTUS. CONCLUSIONS: This review demonstrates that cardiac injuries remain lethal, diagnosis is largely clinical and TTUS may be over-utilized, having little impact on clinical outcome of patients presenting with this injury.

Colorectal anastomotic leakage at the university hospital of the west indies: an analysis of risk factors.

BACKGROUND: Anastomotic leakage remains a concern in general surgical practice. The significance lies in the resultant abdominal sepsis, related morbidity and mortality, risk of anastomotic loss, permanent stoma creation and the effect on local recurrence and overall patient survival in colorectal cancer cases. OBJECTIVES: This study serves to determine the leak rates and the mortality thereof related to colonic and rectal anastomoses at the University Hospital of the West Indies (UHWI) in Kingston, Jamaica. Independent factors contributing to anastomotic leaks in these patients will also be assessed and correlations determined. METHODS: A review of the medical records of one hundred and thirty-three cases of colonic and rectal anastomoses identified retrospectively over a three-year period provided relevant information for analysis. RESULTS: Anastomotic leaks were identified in twelve patients, providing a leak rate of 9.0%. No 30-day mortality related to anastomotic leakage was noted. Based on a multivariate analysis, male gender was identified as the sole independent factor related to anastomotic leakage. CONCLUSION: Colorectal anastomotic leak rates at UHWI fell at the upper limit of leak rates typically quoted in the literature. No modifiable risk factor appeared to contribute to this leak rate. Early identification and intervention is critical in limiting mortality associated with colorectal anastomotic leakage.

Minimally invasive surgery training in the Caribbean--a survey of general surgical residents and their trainers.

BACKGROUND: There has been debate on the feasibility of incorporating minimally invasive surgery (MIS) into surgical practice in developing countries due to resource and training limitations. Our study establishes the current and desired state of MIS training in surgical residency programmes in the Caribbean. METHODS: An adapted version of a previously administered questionnaire was issued to surgeons and residents involved in the general surgical residency programme of The University of the West Indies in Barbados, Jamaica and Trinidad and Tobago. Data were analysed using the Statistical Package for the Social Sciences, version 17.0. RESULTS: The questionnaire was sent to 41 surgeons and 41 residents with a 65% response rate. Most residents had performed less than 25 basic laparoscopic procedures. Up to 82% of residents felt that they would be unable to perform advanced laparoscopic procedures due to lack of training. The principal negative factors influencing MIS training included lack of operating room time, lack of equipment and lack of preceptor expertise. Both surgeons (83.4%) and residents (93.4%) strongly felt that a surgical skills laboratory would be helpful for the acquisition of MIS skills. Both surgeons (85.7%) and residents (100%) felt that there was a role for an MIS surgeon in fulfilling training obligations. CONCLUSION: The basic and advanced MIS experience of residents in the Caribbean is limited. Surgeon training and resource limitations are major contributing factors. There is a strong desire on the part of surgeons and residents alike for the incorporation of more effective MIS training into the residency programme in the Caribbean.

Open abdominal aortic aneurysm repair in the era of endovascular repair.

OBJECTIVES: The development of minimally invasive techniques for abdominal aortic aneurysm (AAA) repair and the establishment of specialized centres have resulted in improved patient outcomes. This study examines open AAA repair at a non-specialized centre where advanced techniques are not practised. METHODS: We conducted a retrospective analysis on a cohort of 83 patients presenting for AAA repair to a non-specialized hospital, the University Hospital of the West Indies (UHWI). The end points assessed included operative (30-day) mortality, postoperative complications, duration of operation, blood loss, intensive care unit (ICU) stay and overall hospital stay. RESULTS: The overall operative mortality was 9.4% (23% for ruptured aneurysms and 5% for unruptured aneurysms). Mean operating time, blood loss, ICU stay and hospital stay were 326 +/- 98 minutes, 2420 +/- 1397 mls, 3 +/- 5 days and 9 +/- 5 days, respectively with no significant differences noted between ruptured and unruptured aneurysms. Mean aneurysm diameter was 6.13 +/- 1.59 cm. CONCLUSION: Mortality rates for open aneurysm repair at the UHWI are consistent with findings in the current literature. Open AAA repair remains a safe treatment option in this environment. Continued improvements need to be made with respect to minimizing blood loss and operation duration, particularly in repairs of unruptured aneurysms.

Duodenal fibrosarcoma mimicking Franz tumour complicated by post-resection chylous ascites.

This case report presents a young woman who underwent a Whipples resection for a large pan-creato-duodenal tumour. Pathology and immunohistochemical analysis of the tumour suggest duodenal fibrosarcoma. The patient's postoperative management was complicated by chylous ascites. A brief literature review is given to highlight this unusual case.

Improving patient outcomes with inguinal hernioplasty-local anaesthesia versus local anaesthesia and conscious sedation: a randomized controlled trial.

PURPOSE: Conscious sedation is regularly used in ambulatory surgery to improve patient outcomes, in particular patient satisfaction. We hypothesized that the addition of conscious sedation would provide greater patient satisfaction with inguinal hernioplasty compared to local anesthesia alone. METHODS: This trial was a single-centre, randomized, placebo-controlled, double-blinded trial where patients undergoing inguinal hernioplasty using local anaesthesia were randomized to receive local anaesthesia alone versus local anaesthesia and conscious sedation. The primary outcome of patient satisfaction was assessed using the Iowa Satisfaction with Anesthesia Scale (ISAS). The study was powered to detect a significant difference in ISAS scores between groups. Comparisons were made using T test and Chi square tests. A p value of less than 0.05 was considered significant. RESULTS: There were 149 patients randomized: 78 to the local anesthesia (LA) group and 71 to the local anaesthesia and conscious sedation (LACS) group. For the primary outcome measure of patient satisfaction, the mean ISAS score was significantly greater in the LACS group (p = 0.009). The experience of pain and pain severity was greater in the LA group (p = 0.016; p = 0.0162 respectively). No statistically significant difference was found between groups with respect to operative time, time to discharge or postoperative complications. CONCLUSION: The use of conscious sedation with local anesthesia for inguinal hernioplasty is safe, results in less pain experience and severity and is associated with better patient satisfaction. The use of conscious sedation does not delay patient discharge.

Hermaphroditism: cytogenetics, gonadal pathology and gender assignment: a case report.

True hermaphroditism is a rare intersex disorder in which individuals possess both testicular and ovarian gonadal tissue. A case of true unilateral hermaphroditism presenting with ambiguous external genitalia, right scrotal testis and left pelvic ovotestis is herein outlined Phallic, gonadal and genetic factors were considered before male gender was assigned. Gender assignment procedures have been questioned by intersex activists opposed to early genital surgery. Western societies have a binary perspective on gender and this leads to a stigma being placed on intersex cases. A multidisciplinary approach to this problem involving paediatric specialists in the field, of endocrinology, surgery and psychiatry is necessary, along with educational programmes that promote tolerance in society to variations in gender.

Topography of spiral ganglion projections to cochlear nucleus during postnatal development in cats.

A fundamenntal organizational principle of the central auditory system is that virtually all areas are tonotopically organized. However, we know very little about the timing or mechanisms that are responsible for the development of this organization. When cats are born, their auditory nervous systems are extremely immature, and their hearing thresholds are very high. Until postnatal days 7-10 (P7-10), cats have behavioral and physiological thresholds which are near or above the pain threshold for adults and also have poor frequency selectivity. Physiological thresholds for auditory nerve fibers and cochlear nucleus neurons are typically above 100-120 dB SPL (sound pressure level re 20 microPa). Three weeks later (at approximately P31), the sensitivity and frequency discrimination (tuning) of these neurons approximate adult values. This study examines the development of the tonotopic projections from the spiral ganglion to the cochlear nucleus during the period in cat development in which the auditory system undergoes the transition from being essentially nonfunctional to having adult-like function. With the animals heavily anesthetized, the cochleas were surgically exposed in kittens ranging in age from P6 to P45. Focal injections of Neurobiotin (NB) were made into Rosenthal's canal, labeling a small cluster of cells in the spiral ganglion of each cochlea. The projections of these labeled cells were visualized as frequency-specific bands of labeled axons and terminals in all major subdivisions of the cochlear nucleus. The thickness of these bands (i.e., the dimension of the bands orthogonal to the isofrequency representation and across the frequency gradient) were measured and compared to similar projections in adults. As in adult cats, the thickness of the bands varied only slightly with the location of the injection site (frequency representation) over a range of 1-7 mm from the cochlear base (45-13 kHz). Moreover, band thickness did not vary significantly with age. These data indicate that the tonotopic organization of spiral ganglion projections to the cochlear nucleus is as precise in kittens as young as P6 as it is in adults.

Intrinsic connections within and between cochlear nucleus subdivisions in cat.

The cat cochlear nuclear complex (CNC) is divided into three major subdivisions: the anteroventral, the posteroventral, and the dorsal cochlear nuclei (AVCN, PVCN, and DCN, respectively). Each of these subdivisions receives a topographic projection from the cochlea and each consists of a number of different cell types. The interconnections between these subdivisions and the cell types which give rise to them were studied by means of small injections of horseradish peroxidase (HRP) made at physiologically identified locations. DCN injections resulted in few labeled cells in the DCN, suggesting that its internal connections are very limited. In contrast, these same DCN injections resulted in numerous labeled cells in the PVCN and AVCN. Labeled PVCN cells, consisting of multipolar, octopus, and small spindle-shaped cells, were located in spatially restricted laminae stretching the entire rostrocaudal length of the nucleus, while labeled AVCN cells consisting of multipolar, globular, small spindle-shaped and small spherical cells were broadly distributed over the posterior half of the nucleus. Similar injections placed in the PVCN resulted in numerous labeled cells in all three subdivisions. The PVCN and AVCN cells labeled after PVCN injections were widely distributed across the isofrequency representations in both nuclei, while the labeled DCN cells were restricted to locations over the injection sites. Injections placed in the posterior half of the AVCN resulted in only very few labeled cells in the DCN. No cells were labeled following injections in the rostral AVCN.

Connections and frequency representation in the auditory brainstem of the mustache bat, Pteronotus parnellii.

The goals of this study were to describe the cochlear frequency map of the mustache bat, Pteronotus parnellii, and to relate the organization of cochlear primary afferents to that of the second-order projections from the cochlear nucleus to the superior olivary complex. Small deposits of horseradish peroxidase (HRP) were placed in the cochlear nucleus at sites that were physiologically characterized with respect to unit-best frequency. From the deposits, labeled fibers were traced in the retrograde direction to the cochlea and in the anterograde direction to the superior olive. Cochleas from both experimental and control animals were examined with light and electron microscopy. The peripheral axons of spiral ganglion neurons were counted in order to quantify the unusual variation in the innervation density along the cochlear spiral of the mustache bat. Regions of increased innervation density were found at the beginning and end of the basal turn of the cochlea. The highest cochlear innervation density consistently occurred in the upper basal turn. In horseradish peroxidase tracing experiments, this region contained labeled fibers only when HRP deposits were made at sites within the cochlear nucleus with unit-best frequencies around 60 kHz. These findings support the suggestion (Kössl and Vater, '85) that the cochlear sites of increased innervation density are related to the neural and behavioral emphasis that this echolocating bat places upon the analysis of the 60 kHz frequency band. The general arrangement of tonotopic maps within the cochlea, cochlear nucleus, and superior olive was consistent with previous observations in this bat and other mammalian species. At all three levels, there was evidence of a disproportionately large representation of frequencies around 60 kHz, similar to the enlarged representation reported within the inferior colliculus and auditory cortex of the mustache bat. In all cases there was a consistent relation between the size of the HRP deposit and the number and distribution of retrogradely labeled neurons in the cochlea. For most cases there was a similar relation between the size of the deposit and the terminal arborization field of anterogradely labeled fibers in the superior olive. However, in cases with deposits associated with the 60 kHz frequency band, the size of the labeled arborization field was more than twice as large as expected from the size of the deposits and from the extent of labeling in the cochlea. These cases suggest that the representation of frequencies around 60 kHz, already overrepresented in both the cochlea and cochlear nucleus, may be further expanded at the level of the superior olivary complex.

Topographic organization of the central projections of the spiral ganglion in cats.

The morphological organization of inputs from restricted sectors of the cat cochlear spiral ganglion into the cochlear nucleus was studied by making focal extracellular injections of horseradish peroxidase (HRP) into the spiral ganglion. Injections resulted in Golgi-like labeling of a small cluster of spiral ganglion cells and their peripheral and central axons. Large injections involved most of the cells within Rosenthal's canal in sectors of the spiral ganglion innervating greater than or equal to 1 mm of the basilar membrane and resulted in narrow, complete laminae of labeled axons and preterminal fields within each cochlear nucleus subdivision. The positions of these bands were consistent with the "isofrequency laminae" appropriate for the frequencies represented at the injection sites, with high frequency laminae situated more dorsally, and lower frequencies progressively more ventral. A discrete projection to the small cell cap area was observed that was discontinuous with the main projection laminae in the ventral cochlear nuclei (VCN). In the dorsal cochlear nucleus, projecting fibers and terminals were excluded from the molecular cell layer. No labeled fibers entered the granule cell areas. In contrast to larger injections, very small HRP deposits labeled only part of an isofrequency lamina. Specifically, injections restricted to the scala tympani aspect of the spiral ganglion labeled only the lateral part of VCN isofrequency laminae, whereas injections limited to the scala vestibuli aspect of the ganglion labeled the medial aspect of the isofrequency planes. Thus these data indicate a previously unrecognized topographic representation of the vertical dimension of the spiral ganglion across VCN isofrequency laminae. Some possible functional implications of this projection organization are discussed.

Spatial organization of inner hair cell synapses and cochlear spiral ganglion neurons.

The morphological organization of the central projections of the cat cochlear spiral ganglion into the cochlear nucleus was previously investigated by creating restricted lesions in the anteroventral cochlear nucleus (AVCN) to ablate selectively either the lateral or the medial aspect of isofrequency projection laminae. Such lesions resulted in highly selective retrograde degeneration of spiral ganglion cells. Ablation of the lateral part of the AVCN caused degeneration of cells within the scala tympani part of the ganglion, whereas medial ablations within the AVCN induced degeneration of the scala vestibuli aspect of the ganglion. The peripheral axons also degenerated and this fiber loss exhibited selective topographies that paralleled the cell loss within the spiral ganglion, although this phenomenon was more prominent in the proximal part of the osseous spiral lamina near the ganglion and less obvious more distally near the habenula perforata. In this investigation, inner hair cells (IHCs) from these selective lesion cases were evaluated by electron microscopy of serial sections through the basal synaptic regions. Results demonstrated differential degeneration of afferent synapses, with greater (but not completely selective) loss of pillar synapses after lateral AVCN lesions and greater loss of modiolar synapses after medial lesions. Because auditory nerve fibers of different spontaneous discharge rates (SRs) have different spatial distributions on the IHC (Liberman, Science 216:1239, 1982), our results suggest that this SR-based organization is maintained in a topographic organization across the vertical (scala tympani-to-scala vestibuli) dimension of the spiral ganglion cell cluster and carried into the ventral cochlear nuclei (VCN). Thus, in addition to the spiral frequency organization represented by the dorsal-to-ventral frequency map in the VCN, there is also an orderly organization of inputs from high- and low-SR fibers across the lateral-to-medial dimension of the VCN such that the lateral isofrequency laminae receive a proportionately greater input from high-SR fibers, whereas medial isofrequency laminae receive preferential input from low- and medium-SR fibers.

Chronic electrical stimulation by a cochlear implant promotes survival of spiral ganglion neurons after neonatal deafness.

This investigation examined the consequences of neonatal deafness and chronic intracochlear electrical stimulation delivered by a cochlear implant during maturation. Kittens were bilaterally deafened by an ototoxic drug administered daily for 2 weeks immediately after birth. Unilateral electrical stimulation was initiated at 7-10 weeks of age and continued over periods of 22-47 weeks (4 hours/day; 5 days/week). Bipolar intracochlear electrodes delivered one of several different electrical signals designed to be temporally challenging to the central auditory system. Morphometric evaluation of spiral ganglion (SG) cell somata within Rosenthal's canal demonstrated a mean of approximately 50% of normal cell density maintained in the chronically stimulated ears, compared with approximately 30% on the control deafened side. This 20% difference in density was highly significant and was greater than differences reported in earlier studies using 30 pps stimulation delivered by either intracochlear bipolar or round window monopolar electrodes. However, the duration of stimulation was also longer in the present study, so it is unclear to what extent the nature of the temporally challenging stimulation vs. its duration contributed to the marked increase in survival. Measurements of the SG cell somata revealed a pronounced decrease in cell diameter in neonatally deafened cats studied about 1 year after deafening, and an additional decrease after long-term deafness (2.5-6.5 years). Furthermore, in the cochlear regions with the greatest stimulation-induced differences in SG cell density, direct measurements of cross-sectional soma area of the largest cells revealed that cells were significantly larger in the stimulated ears. Thus, in addition to the marked increase in the number of surviving SG cells, larger soma area contributed modestly to the pronounced increase in neural density following chronic electrical stimulation.

Quantitative analysis of spiral ganglion projections to the cat cochlear nucleus.

A quantitative examination of the tonotopic organization of primary afferent projections to the cochlear nucleus (CN) in adult cats was conducted by using focal extracellular injections of Neurobiotin (NB) into the spiral ganglion of the basal cochlea. One to three injections separated by intervals of at least 2 mm were positioned along the basal one-third of the cochlea. Each injection produced discrete projection laminae that appeared as parallel horizontal sheets of labeled axons terminals distributed sequentially dorsally to ventrally across each major CN subdivision: the anteroventral, posteroventral, and dorsal cochlear nucleus, (AVCN, PVCN, and DCN, respectively). The length (rostrocaudal dimension), width (mediolateral dimension), thickness (dorsoventral dimension), and relative placement of 18 "frequency-band" laminae were measured in 10 adult cochlear nuclei. The average AVCN projection thickness was approximately twice that of the PVCN and DCN projections. In double injection cases, the center-to-center separation between AVCN laminae was also approximately twice that in the PVCN and equal to that in the DCN. Lamina thickness did not differ significantly as a function of frequency representation. However, in both width and length, mid-frequency laminae were up to two times larger than high-frequency laminae. Thus, the results indicate that DCN projections are the most discrete (i.e., are the thinnest and have the least overlap between adjacent frequency projections), whereas the AVCN projections are the largest but are as discrete as PVCN projections. In addition, high-frequency projections are smaller and more discrete than mild-frequency projections, which are larger and have greater overlap with adjacent frequency projections.

Topographic organization of the cochlear spiral ganglion demonstrated by restricted lesions of the anteroventral cochlear nucleus.

The morphological organization of the central projections of the cat cochlear spiral ganglion into the cochlear nucleus has been investigated by creating restricted lesions in the anteroventral cochlear nucleus (AVCN) in order to ablate selectively either the lateral or the medial aspect of isofrequency projection laminae. Such lesions induced highly selective retrograde degeneration of spiral ganglion cells. Ablation of the lateral part of the AVCN resulted in degeneration of cells within the scala tympani portion of the ganglion, whereas medial lesions within the AVCN induced degeneration of the scala vestibuli portion of the ganglion. Since most, if not all, of the primary afferent axons of the cochlear nerve bifurcate into ascending and descending branches as they enter the brainstem, it is noteworthy that selective damage to the ascending branch in the AVCN was sufficient to induce retrograde degeneration of the spiral ganglion cell somata. The peripheral and central axons also degenerated, and the losses of both the radial nerve fibers in the osseous spiral lamina and the central axons passing into the modiolus displayed selective topographies that paralleled the cell loss within the spiral ganglion. The results of this study support our previous hypothesis, based upon earlier horseradish peroxidase labeling experiments, that there is a topographic organization to the projection of the spiral ganglion within the isofrequency laminae that is orthogonal to the frequency representation within the ventral cochlear nuclei (VCN). That is, in addition to the spiral frequency organization of the ganglion, represented by the dorsal-to-ventral frequency map in the VCN, there is also an orderly and sequential distribution of inputs from the vertical (scala tympani-to-scala vestibuli) dimension of the spiral ganglion across the lateral-to-medial axis of the VCN. The interaction of these two topographic representations, distributed across the three dimensions of the VCN, must partly define the selective and/or integrative neuronal response properties at this first level of central nervous system processing of auditory signals within the cochlear nuclei.

Uptake of horseradish peroxidase from perilymph by cochlear hair cells.

The specific mechanisms involved in the uptake of an exogenous protein, horseradish peroxidase (HRP), by cochlear hair cells were studied morphologically in light and electron microscopy. HRP was internalized by coated vesicles which formed from the plasma membrane only in the basal portion of the hair cells. Inner hair cells demonstrated relatively greater uptake than adjacent outer hair cells. The lateral plasma membrane of outer hair cells was unique in that reaction product was never bound to this portion of the membrane. Subsequent to endocytosis, HRP was transported to the Golgi and its associated system of endoplasmic reticulum and lysosomes. The exogenous protein was sequestered in a striking accumulation of secondary lysosomes and multivesicular bodies which were restricted to the infracuticular region of the hair cells and persisted for periods of at least 72 h after introduction of HRP. It is not clear whether the hair cells were slowly degrading the HRP or if the lysosomal enzymes necessary for its breakdown were lacking. The pathway demonstrated by HRP uptake and intracellular transport may represent one route by which macromolecules requisite for basic metabolic or nutritional requirements of the hair cells are supplied from the perilymph.

Cochlear pathology of long term neomycin induced deafness in cats.

The long term sequelae of hair cell destruction consequent from administration of the ototoxic aminoglycoside antibiotic, neomycin sulfate, were evaluated in histological and ultrastructural studies of cochlear morphology in cats. Complete hearing loss, as defined by an absence of brainstem evoked responses to click stimulation at 120 dB peak SPL, was induced by intramuscular injections of neomycin at 50 mg/kg body weight/day, and cochlear pathology was studied at 6 months and 1, 3 and 4 years following onset of profound deafness. In these long term ototoxicity cases the organ of Corti was collapsed and resorbed over the basal one-quarter to three-quarters of the cochlear spiral, depending on duration of deafness. Significant progressive reduction in the spiral ganglion cell population and sequential degenerative alterations in the remaining neurons were observed with increasing time elapsed after induced hearing loss. The sequence of pathological alterations in spiral ganglion neurons appeared to be: a) swelling, demyelination and degeneration of the peripheral dendrites; b) demyelination and shrinkage of the cell soma with preservation of the central axon; and c) demyelination of the central axon and degeneration of the cell perikaryon. In apical cochlear regions, severe degeneration of the spiral ganglion preceded the collapse of the tunnel of Corti and regional loss of pillar cells. Residual populations of spiral ganglion neurons were as low as 1-2% of the normal values in the most severely degenerated cochleae in the series. Light microscopic and ultrastructural studies revealed a selective survival advantage for the unmyelinated type II neurons over the myelinated type I neurons with these long survival periods. The prolonged time course and atrophic nature of these pathological alterations suggests that degeneration of spiral ganglion neurons progresses continuously following drug-induced insult to the cochlea. Some possible factors contributing to this long term progressive degeneration will be discussed.

Postnatal development of the organ of Corti in cats: a light microscopic morphometric study.

This study quantitatively characterizes the development of the major morphological features of the organ of Corti during the first 2 weeks postnatal, the period when the cat auditory system makes the transition from being essentially non-functional to having nearly adult-like responses. Four groups of kittens (n = 3) were studied at one day postnatal (P1), P5, P10, P15, and compared to adults. Measurements were made of the organ of Corti at 3 cochlear locations: 20%, 60% and 85% of basilar membrane length from the base cochlear locations which in the adult correspond to best frequencies of approximately 20 kHz, 2 kHz and 500 Hz, respectively. In addition, measurements of basilar membrane length and opening of the tunnel of Corti were made in 20 cochlear specimens from kittens aged P0-P6. Results indicate that: (i) at P0 the basilar membrane has attained adult length, and the tunnel of Corti is open over approximately the basal one-half of the cochlea; (ii) the initial opening of the tunnel of Corti occurs at a site about 4 mm from the cochlear base (best frequency of approximately 25 kHz in the adult cochlea); (iii) the thickness of the tympanic cell layer decreases markedly at the basal 20-kHz location; (iv) the areas of the tunnel of Corti and space of Nuel and the angulation of the inner hair cells (IHC) relative to the basilar membrane all show marked postnatal increases at both the middle and apical locations; (v) IHC are nearly adult-like in length and shape at birth, whereas the OHC (at 2-kHz and 500-Hz locations) undergo marked postnatal changes; (vi) disappearance of the marginal pillars and maturation of the supporting cells are not yet complete by P15.

Does exogenous GM1 ganglioside enhance the effects of electrical stimulation in ameliorating degeneration after neonatal deafness?

This study examined the combined effects of administration of exogenous GM1 ganglioside and electrical stimulation on the cochlear nucleus (CN) of cats deafened neonatally by ototoxic drugs. Five normal hearing adult cats served as controls. Another 12 cats were deafened bilaterally by daily injections of neomycin sulfate (60 mg/kg) for 17-21 days after birth until auditory brainstem testing demonstrated profound hearing loss. Six of the deaf animals comprised the GM1 group, which received daily injections of GM1 ganglioside (30 mg/kg) for 28-38 days during the period after profound deafness was confirmed, and prior to receiving a cochlear implant. The non-GM1 group (n=6) received no treatment during this interim period. All the deafened animals underwent unilateral cochlear implantation at 6-9 weeks postnatal and received several months (mean duration, 32 weeks) of chronic electrical stimulation (4 h/day, 5 days/week). Stimulation was delivered by intracochlear bipolar electrodes, using electrical signals that were designed to be temporally challenging to the central auditory system. Results showed that in the neonatally deafened animals, both the GM1 and non-GM1 groups, the volume of the CN was markedly reduced (to 76% of normal), but there was no difference between the animals that received GM1 and those that did not. The cross sectional areas of spherical cell somata in both GM1 and non-GM1 groups also showed a highly significant reduction in size, to < or =75% of normal after neonatal deafening. Moreover, in both the GM1 and non-GM1 groups, the spherical cells in the CN ipsilateral to the implanted cochlea were significantly larger (6%) than cells in the control, unstimulated CN. Again, however, there was no significant difference between the GM1 group and the non-GM1 group in spherical cell size. These results contrast sharply with previous reports that exogenous GM1 prevents CN degeneration after neonatal conductive hearing loss and partially prevents spiral ganglion cell degeneration when administered immediately after ototoxic drug deafening in adult animals. Taken together, findings to date suggest that GM1 may be effective in preventing degeneration only if the GM1 is administered immediately at the time hearing loss occurs.