Synaptic events and discharge patterns of cochlear nucleus cells. I. Steady-frequency tone bursts.

Unitary discharge patterns (peristimulus time histograms or PSTH) and synaptic events were studies with intracellular recording techniques in 164 cat cochlear nucleus cells to steady-frequency tone bursts 250 ms in duration. There were four response types defined on the basis of the shape of the discharge patterns to tones at the characteristic or best frequency. Primarylike units resemble eighth nerve fibres and have a maximum discharge at tone onset, followed by a smooth decline to a steady level of activity. Buildup units have a transient response at tone onset, followed a period of little or not activity before gradually increasing their discharge rate for the remainder of the tone burst. Onset units have an initial burst of spikes at the onset, with little or no activity for the remainder of the tone burst. Pause units have a long latency (10-30 ms) between tone onset and the appearance of low levels of unit activity, which then gradually increase in rate for the remainder of the tone burst. Changes in signal frequency or intensity within the excitatory response area did not modify response patterns of primarylike and onset units, but could evoke primarylike patterns in buildup and pause units. Inhibition manifested by suppression of spontaneous activity and membrane hyperpolarization were of three kinds: 1) in response to signals at the edges of the excitatory response area (i.e., the inhibitory surround) and detected in onset buildup, and pause units but not in primarylike units; 2) occurring at the offset of tones in the excitatory response area and detected in all four types of cochlear nucleus cells; 3) during excitatory tone bursts in onset and buildup units associated with the periods of suppressed unit activity. Membrane hyperpolarization did not accompany the delay in unit activity after tone onset in pause units. Inhibitory events in cochlear nucleus cells provide mechanisms for producing diversity in the temporal pattern of discharges to acoustic signals which may underly the encoding of complex features of sounds.     

Implementing a Stratified Vocational Advice Intervention for People on Sick Leave with Musculoskeletal Disorders: A Multimethod Process Evaluation

Journal of Occupational Rehabilitation - Purpose To perform a process evaluation of a stratified vocational advice intervention (SVAI), delivered by physiotherapists in primary care, for people on...     

Pressure Transfer Between Intracranial and Cochlear Fluids in Patients With Meniere's Disease

Objectives: To elucidate the pressure transfer between intracranial and labyrinthine fluids in patients with well‐defined unilateral Meniere's disease. Study Design: Eleven patients previously exposed to hypobaric pressure agreed to be investigated further with the tympanic membrane displacement (TMD) technique. TMD was used to indirectly analyze perilymph pressure changes as the result of changes in body position. Methods: Repeated measurements for both the diseased and the healthy ears were made with the patients supine and then in a sitting position. The TMD parameters for the maximum inward displacement, the Vi, and the mean volume displacement, the Vm, were calculated and compared. Results: The paired comparison showed statistically significant larger Vi values for both ears in the supine position. A similar tendency was observed for the Vm value. This difference of the Vi was significantly larger for the diseased ear compared with the currently healthy ear. The results were compared to the audiometric and electrocochleographic results previously obtained on the same patients when they were subjected to hypobaric pressure. Patients who experienced the largest differences in hearing level thresholds in the lower frequencies also showed the greatest differences in TMD values as the result of postural changes. Conclusions: Despite the limited number, the statistically supported results suggest a relation between the efficiency of the routes of pressure transfer and the observed effect of hypobaric exposure. The results also indicate that for the patients tested, the routes of communication are more effective in the diseased ear than in the healthy ear—a condition that may relate to the pathogeneses of Meniere's disease.     

Mosaic pathogenic variants in AKT3 cause capillary malformation and undergrowth

Capillary malformations are slow-flow vascular malformations that affect the microcirculation including capillaries and post capillary venules and can be associated with growth differences. Specifically, the association of capillary malformations with undergrowth is a vastly understudied vascular syndrome with few reports of genetic causes including PIK3CA, GNAQ, and GNA11. Recently, a somatic pathogenic variant in AKT3 was identified in one child with a cutaneous vascular syndrome similar to cutis marmorata telangiectatica congenita, undergrowth, and no neurodevelopmental features. Here, we present a male patient with a capillary malformation and undergrowth due to a somatic pathogenic variant in AKT3 to confirm this association. It is essential to consider that mosaic pathogenic variants in AKT3 can cause a wide spectrum of disease. There is a need for future studies focusing on capillary malformations with undergrowth to understand the underlying mechanism.     

Randomized clinical trial of the 350-mm2 versus the 500-mm2 Baerveldt implant: longer term results: Is bigger better?

OBJECTIVE: To report the longer term results of a randomized, clinical trial comparing the 350-mm2 and the 500-mm2 Baerveldt glaucoma implants. DESIGN: Extended follow-up on a randomized, controlled trial. PARTICIPANTS: Between March 1991 and April 1993, 107 patients with uncontrolled intraocular pressure (IOP) due to non-neovascular glaucoma associated with aphakia, pseudophakia, or failed filters were randomly assigned for surgical placement of either the 350-mm or the 500-mm2 Baerveldt implant at the Doheny Eye Institute. METHODS: A random-numbers table was used to assign each patient to one of the two groups. Preoperative IOPs and visual acuities were recorded. Clinical records were reviewed to ascertain postoperative IOPs, visual acuities, number of medications used, and implant-related complications that occurred throughout the follow-up period. MAIN OUTCOME MEASURES: Success was defined as IOP of 6 mmHg or greater and of 21 mmHg or less in two or more consecutive follow-up visits without further glaucoma surgery or loss of light perception attributable to glaucoma. RESULTS: The overall success rates were 87% for the 350-mm2 group and 70% for the 500-mm2 group (P = 0.05). Average follow-up was 37 months (range, 1-76 months) for the 350-mm2 group and 34 months (range, 5-77 months) for the 500-mm2 group. The life-table success rates declined over time for both implant groups, from a high of 98% for the 350-mm2 group and 92% for the 500-mm2 group at 1 year to a cumulative success rate of 79% for the 350-mm2 group and 66% for the 500-mm2 group at 5 years. Visual acuities were better or remained the same in 50% of the patients in the 350-mm2 group and 46% of those in the 500-mm2 group. Complications during the 5-year follow-up were also statistically similar. CONCLUSIONS: The longer term results show that the 350-mm2 Baerveldt implant is more successful than the 500-mm2 implant for overall IOP control. Interval comparisons indicate a higher rate of success for the 350-mm2 implant in the first, second, third, fourth, and fifth years of implantation. Visual acuities, implant-related complications, and average IOPs were statistically indistinguishable between the two groups.     

Long-term use of diazepam

Plasma concentrations of diazepam and its major active metabolite nordiazepam were measured in 108 neurosurgical patients taking diazepam in doses of 5 to 40 mg/day for periods from one month to 16 years. Diazepam was used for relief of pain or muscle spasm, or anxiety and sleeplessness associated with these two symptoms, and was considered to be beneficial by 83% of the patients, although use of other drugs confounded this evaluation. Concentrations of total diazepam-nordiazepam ranged from 0 to 2,584 ng/mL, with nordiazepam being the predominant metabolite. "Low" concentrations (less than 250 ng/mL) were found in 35 of the 108 patients, with 19 having concentrations lower than 100 ng/mL. "High" concentrations (greater than 900 ng/mL) were found in 20 patients and did not occur more frequently than in other studies of long-term diazepam ingestion. Even with long-term use, diazepam seemed to retain its efficacy and did not lead to any clear-cut abuse.     

Intracellular uptake and cytotoxic effect in vitro of doxorubicin and epirubicin in human leukemic and normal hematopoietic cells

Summary Leukemic cells from patients presenting with acute nonlymphoblastic leukemia and normal hematopoietic bone marrow cells from healthy donors for allogeneic bone marrow transplantation were incubated for 3 h with doxorubicin and epirubicin at different concentrations. The intracellular uptake at the end of the incubation was determined by photofluorometry in leukemic cells from 15 patients and in normal cells from 9 donors for bone marrow transplantation. Cytotoxicity in vitro against granulocyte/macrophage colony-forming units (CFU-GM) was determined in normal cells from 7 donors, and in vitro toxicity against leukemic cells was determined by a clonogenic technique in cells from 6 patients and by vital dye staining (DiSC) following 4 days' culture in cells from 15 patients. Epirubicin was significantly less toxic than doxorubicin to normal hematopoetic cells (72%±20% survival of cells for epirubicin vs 45%±13% for doxorubicin at a concentration of 0.2 m;P0.005). As analyzed by the DiSC assay, 0.2 m epirubicin was slightly more toxic to leukemic cells than was the same concentration of doxorubicin (47% vs 61% survival,P0.01), but the clonogenic assay revealed no difference in toxicity to leukemic cells. At a concentration of 0.2 m, the mean intracellular uptake of epirubicin in leukemic cells was 0.43±0.26 nmol/mg protein as compared with 0.33±0.14 nmol/mg protein for doxorubicin (not significant). In normal cells, the uptake of epirubicin at a concentration of 0.2 m was 0.47±0.25 nmol/mg protein as compared with 0.31±0.21 nmol/mg protein for doxorubicin (not significant). The reduced myelotoxicity observed in vitro together with the retained toxicity to leukemic cells indicates that the therapeutic index of epirubicin is better than that of doxorubicin.     

Rectus muscle orbital wall fixation: a reversible profound weakening procedure.

INTRODUCTION: Surgical treatment of third nerve palsy, sensory exotropia and strabismus secondary to anomalous innervation of the rectus muscles, frequently require large rectus muscle recessions in an attempt to maintain alignment in the primary position and reduce the effects of misinnervation. The aim of this study was to describe and evaluate the results of inactivation of a rectus muscle by its attachment to the adjacent orbital wall. METHODS: Seven subjects diagnosed with third-nerve palsy (three cases), Duane syndrome (two cases), sensory exotropia (one case), and congenital aberrant innervation of vertical rectus muscles (one case) underwent rectus muscle inactivation by orbital wall fixation. The rectus muscle was disinserted from the globe and reattached to the adjacent orbital periosteum using non-absorbable sutures. This surgery was performed on the lateral rectus muscle in six subjects, and surgery was performed on both ipsilateral vertical rectus muscles in one. RESULTS: Postoperatively four of six patients were aligned within 12 prism diopters of orthotropia in primary position. All patients had improvement of the anomalous head posture. In Duane syndrome, lateral rectus inactivation markedly reduced co-contraction and globe retraction. No overcorrections resulted. CONCLUSION: A rectus muscle may be functionally inactivated when its insertion is attached to the orbital periosteum. Advantages of this procedure over extirpation and free tenotomy include permanent disinsertion of the muscle from globe and reversibility.     

Matching risk and resources in high-risk pregnancies.

OBJECTIVE: To evaluate the joint impact of pregnancy risk and the timing of referral of high-risk pregnancies from obstetricians to maternal fetal medicine (MFM) sub-specialists on gestational age (GA) at delivery. METHODS: For the period 1992-2002, 2567 consecutive deliveries from pregnancies of at least 23 weeks gestational age (GA) from a community-level sub-specialty perinatal center were studied. A multiple regression model was developed specifying the impact of various risk factors and referral timing. RESULTS: Prior pregnancy risk was inversely related to GA at birth. Referral timing, operationalized as a continuous variable, did not have a significant additive impact on GA at birth, but several dummy-variable interaction effects combining risk factors and referral before 20 weeks as a dichotomy were significant. CONCLUSION: There are identifiable risks that occur either before the pregnancy or early into it that should lead to early referral to a sub-specialist because of their impact on GA at birth. Early referral is an important tactic in a larger preterm prevention strategy, but it needs to be embedded in a broader maternal-fetal health initiative in which both generalists and sub-specialists play important roles.