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Background: The serotonin and noradrenaline (norepinephrine) reuptake inhibitor duloxetine has been approved in the US and elsewhere for a number of indications, including psychiatric illnesses and chronic pain conditions. Because the patient populations are diverse within these approved indications, and duloxetine is not yet approved for treatment of other conditions, we wanted to determine if adverse event profiles would differ among patients being treated for these various conditions.Objective: To provide detailed information on the adverse events associated with duloxetine and to identify differences in the adverse event profile between treatment indications and patient demographic subgroups.Methods: Data were analysed from all placebo-controlled trials of duloxetine completed as of December 2008. The 52 studies included 17,822 patients (duloxetine n = 10,326; placebo n = 7496) with major depressive disorder, generalized anxiety disorder, diabetic peripheral neuropathic pain, fibromyalgia, osteoarthritis knee pain (OAKP), chronic lower back pain and lower urinary tract disorders. The main outcome measures were rates of treatment-emergent adverse events (TEAEs) and adverse events reported as the reason for discontinuation.Results: The overall TEAE rate was 57.2% for placebo-treated patients and 72.4% for duloxetine-treated patients (p < or = 0.001). Patients with OAKP had the lowest TEAE rate (placebo 36.7% vs duloxetine 50.2%, p < or = 0.01), while patients with fibromyalgia had the highest rate (placebo 80.0% vs duloxetine 89.0%, p < or = 0.001). The most common TEAE for all indications was nausea (placebo 7.2% vs duloxetine 23.4%, p < or = 0.001), which was predominantly mild to moderate in severity. No statistically significant treatment-by-subgroup interactions for age were found between placebo and duloxetine treatment for the most common TEAEs. The rates of duloxetine-associated dry mouth and fatigue were greater in women than in men (13.1% vs 10.4%, interaction p = 0.004; and 9.4% vs 7.6%, interaction p = 0.03, respectively). Duloxetine-associated dry mouth incidence was higher in Caucasians than non-Caucasians (13.2%, 11.0%, interaction p = 0.04).Conclusions: Duloxetine treatment is associated with significantly higher rates of common TEAEs versus placebo, regardless of indication or demographic subgroup. Differences across indications are likely to be attributable to the underlying condition rather than duloxetine, as suggested by the similar trends observed in placebo- and duloxetine-treated patients. [ABSTRACT FROM AUTHOR]

Introduction: We have recently shown that readmission after EGS procedures carries a 4-fold higher mortality rate when compared to those not readmitted. Understanding factors associated with death after readmission is paramount to improving outcomes for EGS patients. We aimed to identify risk factors contributing to failure-to-rescue (FTR) during readmission after EGS. We hypothesized that most post-readmission deaths in EGS are attributable to FTR., Methods: A retrospective cohort study using the NSQIP database 2013-2019 was performed. Patients who underwent 1 of 9 urgent/emergent surgical procedures representing 80% of EGS burden of disease, who were readmitted within 30 days post-procedure were identified. The procedures were classified as low- and high-risk. Patient characteristics analyzed included age, sex, BMI, ASA score comorbidities, postoperative complications, frailty, and FTR. The population was assessed for risk factors associated with mortality and FTR by uni- and multivariate logistic regression., Results: Of 312,862 EGS cases, 16,306 required readmission. Of those, 10,748 (3.4%) developed a postoperative complication. Overall mortality after readmission was 2.4%, with 90.6% of deaths attributable to FTR. Frailty, high-risk procedures, pulmonary complications, AKI, sepsis, and the need for reoperation increased the risk of FTR., Discussion: Death after a complication is common in EGS readmissions. The impact of FTR could be minimized with the implementation of measures to allow early identification and intervention or prevention of infectious, respiratory, and renal complications., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Intimate partner violence (IPV) is a significant cause of injury, and in pregnant patients (PIPV) poses a risk to both mother and fetus. Characteristics and outcomes for PIPV patients have not been well described. We hypothesize that PIPV patients have higher admission rates and mortality than non-IPV pregnant trauma (PT) patients and nonpregnant female IPV patients of childbearing age. We also hypothesize differences exist between PIPV and PT patient injury patterns, allowing for targeted IPV screening., Study Design: The Nationwide Emergency Department Sample database was queried from 2010 to 2014 to identify IPV in adult women patients by injury code E967.3. Patients were compared in 2 ways, PIPV vs PT and PIPV vs nonpregnant female IPV patients. Demographics, injury mechanisms, and National Trauma Data Standard injury diagnoses were surveyed. Primary outcomes were hospital admissions and mortality. Logistic regression was used to estimate risk factors of the outcomes of hospitalization and IPV victimization in pregnant injured patients., Results: There were 556 PIPV patients, 73,970 PT patients, and 56,543 nonpregnant female IPV patients. When comparing PIPV to PT, more PIPV patients had Medicaid coverage or were self-pay. Suffocation, head injuries, face/neck/scalp contusions, multiple contusions, and abrasions/friction burns were more prevalent in PIPV patients. Mortality and hospital admissions were scarce among all cohorts. Predictors of IPV victimization among injured pregnant patients include multiple injuries, head injuries, face/neck/scalp contusions, abrasions/friction burns, contusions of multiple sites, and those with Medicaid or self-pay coverage., Conclusions: Among injured pregnant patients, those with multiple injuries, head injuries, contusions of the face/neck/scalp, abrasions/friction burns, and multiple contusions should undergo IPV screening. Admissions and mortality are low; therefore, prevention measures should be implemented in the emergency department to reduce repeat victimization., (Copyright © 2022 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: Current guidelines recommend that patients with choledocholithiasis undergo same-admission cholecystectomy. The compliance with this guideline is poor in elderly patients. We hypothesized that elderly patients treated with endoscopic retrograde cholangiopancreatography (ERCP) alone would have higher complication and readmission rates than the patients treated with cholecystectomy., Methods: The Nationwide Readmissions Database was queried for all patients aged ≥65 years with admission for choledocholithiasis January to June 2016. The patients were divided based on index treatment received: (1) no intervention; (2) ERCP alone; or (3) cholecystectomy. Multivariate analyses identified predictors of cholecystectomy during index admission and of readmissions., Results: A total of 16,121 patients with choledocholithiasis were admitted; 38.4% underwent cholecystectomy, 37.6% endoscopic retrograde cholangiopancreatography alone, and 24.0% no intervention. The patients not receiving a cholecystectomy were more likely to be older, female, have a higher Elixhauser score, do-not-resuscitate status, and at a teaching hospital (all P < .001). Emergency readmissions for recurrent biliary disease were lowest in patients undoing a cholecystectomy (2.2% vs 9.2% endoscopic retrograde cholangiopancreatography and 12.4% no intervention, P < .001), as were readmissions for complications (3.6% vs 5.5% and 7.8%, P < .001). Cholecystectomy reduced rates of readmissions for recurrent disease (odds ratio 0.168, P < .001), for complications (odds ratio 0.540, P < .001), and death during readmission (odds ratio 0.503, P = .007); endoscopic retrograde cholangiopancreatography alone reduced only rates of readmissions. Age was not a predictor of readmission or death., Conclusion: Index admission cholecystectomy is associated with a lower risk of readmission for biliary disease or complications, as well as death during readmission, in elderly patients. Age alone is not predictive of outcomes; surgical intervention should be guided by clinical condition, comorbidities, and patient preference., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Surgical residency training requires Advance Care Planning (ACP) and Palliative Care (PC) education. To meet education needs and align with American College of Surgeons guidelines, our Surgical Intensivists and PC faculty developed courses on communication and palliation for residents (2017-18) and fellows (2018-19). We hypothesized that education in ACP would increase ACP communication and documentation., Methods: The trauma registry of an academic, level 1trauma center was queried for ICU admissions from 2016-2019, excluding incarcerated and pregnant patients. A retrospective chart review was performed, obtaining frequency of ACP documentation, ACP meetings, time from admission to documentation, and PC consultation. We collected ICU quality measures as secondary outcomes: ICU Length Of Stay (LOS), hospital LOS, ventilator days, invasive procedures, discharge disposition, and mortality. Comparisons were made between years prior to (Y 1) and following implementation (Y 2: residents, Y 3: fellows)., Results: For 1732 patients meeting inclusion criteria, patient demographics, injuries, and injury severity score were comparable. ACP documentation increased from 19.5% in Y 1 to 57.2% in Y 3 (P < 0.001). Time to ACP documentation was reduced from 47.6 to 13.1 h (P < 0.001) from time of admission. ICU LOS decreased from 6 to 4.8 d (P = 0.004). Patients in Y 3 had fewer tracheostomies and percutaneous endoscopic gastrostomies. PC consultations decreased. Mortality was unchanged., Conclusion: Following trainee education, we observed increases in ACP documentation, earlier communication and improvements in ICU quality measures. Our findings suggest that trainee education positively impacts ACP documentation, reduces LOS, and improves trauma critical care outcomes., (Copyright © 2021. Published by Elsevier Inc.)

Breast conservation therapy (BCT) has a reported incidence of positive margins ranging widely in the literature from 20% to 70%. Efforts have been made to refine standards for partial mastectomy and to predict which patients are at highest risk for incomplete excision. Most have focused on histology and demographics. We sought to further define modifiable risk factors for positive margins and residual disease. A retrospective study was conducted of 567 consecutive partial mastectomies by 21 breast and general surgeons from 2009 to 2012. Four hundred fourteen cases of neoplasm were reviewed for localization, intraoperative assessment, excision technique, rates, and results of re-excision/mastectomy. Histologic margins were positive in 23% of patients, 25% had margins 0.1-0.9 mm, and 7% had tumor within 1-1.9 mm. Residual tumor was identified at-in 61 cases: 38% (disease at margin), 21% (0.1-0.9 mm), and 14% (1-1.9 mm). Ductal carcinoma in situ (DCIS) was present in 85% of residual disease on re-excision and correlated to higher rates of re-excision (p = <0.001), residual disease, and subsequent mastectomy. The use of multiple needles to localize neoplasms was associated with 2-3 times the likelihood for positive margins than when a single needle was required. The removal of additional margins at initial surgery correlated with improved rates of complete excision when DCIS was present. Patients must have careful analysis of specimen margins at the time of surgery and may benefit from additional tissue excision or routine shaving of the cavity of resection. Surgeons should conduct careful patient selection for BCT, in the context of multifocal, and multicentric disease. Patients for whom tumor localization requires bracketing may be at higher risk for positive margins and residual disease and should be counseled accordingly., (© 2016 Wiley Periodicals, Inc.)

Patients who choose care in a home setting at the end of life may be at risk because of their declining cognitive or physical abilities, environmental hazards in the home, or caregiving issues. Although safety concerns in hospitals have been well documented, knowledge about safety issues in the home setting is limited. This qualitative, focused-ethnographic study was conducted to understand the safety issues that occur in the home setting from the perspective of home care clinicians who manage these issues for end-of-life patients.

Background: A basic tenet of palliative care is to maintain an individual's control over the dying process. However, when decline occurs quickly, as may be the case in advanced cancer, transition of responsibility for illness management to a family caregiver may become necessary when care takes place in the home., Objective: The aim of this study was to understand the decision-making process that occurs between a dying individual and his or her family caregiver., Methods: Participants in this grounded theory study were selected by purposive and theoretical sampling methods. Data were collected and analyzed using a constant comparison approach., Results: The core category covering captured the inordinate efforts taken by informal caregivers to ensure that their family member would be able to die in the manner of his or her choosing. The basic social process, dancing on the stairs, chronicled the families' decision-making process as they navigated through this delicate and precarious end stage of life., Conclusions: Dancing on the stairs required a close relationship between 2 people who were willing to remain engaged with each other, despite the difficulties they faced. This decision-making process may be applicable to other health care transitions in people's lives that need to be managed with another person., Implications for Practice: Palliative care education for nurses in all care health settings may ease transitions for end-stage patients. Health promotion initiatives designed to educate the lay public about advance directives and end-stage illness management in a home setting may help to prepare family caregivers for their future responsibilities.

Objective: The objective of this study is to compare olanzapine with ziprasidone therapy in patients with schizophrenia or schizoaffective disorder and experiencing depressive symptoms., Methods: This randomized, double-blind, 24-week, fixed-dose study compared olanzapine (n = 202) and ziprasidone (n = 192) for patients with schizophrenia or schizoaffective disorder and experiencing prominent depressive symptoms. Outcome measures included change in Calgary Depression Scale for Schizophrenia (CDSS) score from baseline to 8 weeks (primary outcome) and changes in CDSS, Montgomery-Asberg Depression Rating Scales, Positive and Negative Syndrome Scale, and Global Assessment of Functioning (GAF) scores for 24 weeks. Statistical analyses included mixed-effects model repeated measures (primary analysis) and change from baseline to last observation carried forward (LOCF)., Results: At baseline, patients had moderate depressive symptoms (mean Montgomery-Asberg Depression Rating Scales total score, 27.3). For 8 weeks, patients treated with olanzapine or ziprasidone had significant improvements on CDSS. Treatment group differences were not statistically significant (P = 0.493, mixed-effects model repeated measures; P = 0.497, LOCF). For 24 weeks, olanzapine-treated patients showed significantly greater improvements in depressive symptoms (results varied by depression measure and statistical approach) and GAF (P < 0.017, LOCF). A significantly higher proportion of olanzapine-treated patients completed the study (44.6% vs 29.7%; P = 0.003) and remained longer on medication (median, 163 vs 73 days, P < 0.001), compared with ziprasidone-treated patients. Olanzapine-treated patients experienced significantly (P < 0.05) greater increases in triglycerides, HgbA1c, and weight., Conclusions: For 24 weeks, olanzapine-treated patients had greater and more sustained participation in treatment, during which time significantly greater improvements were observed in depressive symptoms and GAF scores, along with increases in weight and certain metabolic parameters as compared with ziprasidone-treated patients.

Long QT syndrome (LQTS) is a heterogeneous disorder caused by mutations of at least five different loci. Three of these, LQT1, LQT2, and LQT5, encode potassium channel subunits. LQT3 encodes the cardiac-specific sodium channel, SCN5A. Previously reported LQTS-associated mutations of SCN5A include a recurring three amino acid deletion (DeltaKPQ1505-1507) in four different families, and four different missense mutations. We have examined the SCN5A gene in 88 index cases with LQTS, including four with Jervell and Lange-Nielsen syndrome and the remainder with Romano-Ward syndrome. Screening portions of DIII-DIV, where mutations have previously been found, showed that none of these patients has the three amino acid deletion, DeltaKPQ1505-1507, or the other four known mutations. We identified a novel missense mutation, T1645M, in the DIV; S4 voltage sensor immediately adjacent to the previously reported mutation R1644H. We also examined all of the additional pore-forming regions and voltage-sensing regions and discovered another novel mutation, T1304M, at the voltage-sensing region DIII; S4. Neither T1645M nor T1304M were seen in a panel of unaffected control individuals. Five of six T1304M gene carriers were symptomatic. In contrast to previous studies, QT(onset-c) was not a sensitive indicator of SCN5A-associated LQTS, at least in this family. These data suggest that mutations of SCN5A are responsible for only a small proportion of LQTS cases., (Copyright 1999 Wiley-Liss, Inc.)

Adult physiological properties of cat superior colliculus cells develop gradually during the first two months of life. Since many of the neuronal properties in the adult cat appear to depend upon the integrity of visual cortex, it was postulated that the maturation of superior colliculus cells is, in large part, a reflection of corticotectal maturation. An attempt was made to study the development of the corticotectal pathway with the autoradiographic tracing technique. Injections of [3H]leucine were made in the visual cortex of kittens 6 h to 12 days of age and animals were sacrificed 20-24 h later. A dense projection from visual cortex to the superior colliculus and to the lateral geniculate nucleus was noted in all animals. Both projections appeared to be topographically organized. In addition, cortical projections to the lateral posterior-pulvinar region and sparse projections to the contralateral visual cortex were noted. Two, non-mutually exclusive, explanations for the presence of a corticotectal pathway in the absence of mature cell properties in the superior colliculus are most apparent: (a) corticotectal synapses are incompletely formed at birth and require many weeks to develop, and (b) corticotectal cells are immature during early postnatal life and cannot impress adult-like characteristics upon the superior colliculus cells until they, themselves, 'mature'.

A child was treated for thoracoabdominal ectopia cordis and an associated chromosomal defect. Contrary to most cases in which death is due to the externally situated heart and abdominal viscera, this patient died from congenital heart disease.

Direct and indirect projections from the cat superior colliculus to the extraocular motor nuclei were studied using the orthograde autoradiographic tracing method, the retrograde horseradish peroxidase technique, and Golgi methods. The results show that the superior colliculus projects to the central gray matter directly overlying the oculomotor complex. This projection arises almost entirely from the rostral third of the colliculus, and it terminates most heavily over the rostral half of the oculomotor complex. Dendrites of oculomotor cells extend into this tectal termination zone, making direct tecto-oculomotor contacts possible. Central gray cells within this termination zone project bilaterally to the abducens nuclei. It is proposed that the superior colliculus projection to the supraoculomotor central gray matter and the projection from the central gray matter to the abducens nuclei play a role in convergent eye movements. The superior colliculus projects lightly to a cell group directly ventrolateral to the trochlear nucleus. The superior colliculus sends a small direct projection to the contralateral abducens nucleus and a substantial projection to wide regions of the reticular formation that have been shown previously to project, in turn, to the abducens nucleus. Colliculus cells projecting to the abducens nucleus and adjacent reticular formation are located only in the caudal three-fourths of the colliculus, where they become increasingly concentrated at successively more caudal levels. It is proposed that the graded density of the cells of origin of this projection is the basic structural mechanism by which the colliculus generates horizontal foveating saccades of different amplitudes. Laminar analysis of the origin of all the superior colliculus projections to the extraocular motor regions described here revealed that they arise mostly from the stratum griseum intermedium.

Substantial corticotectal (and corticothalamic) projections from the cortex of the anterior ectosylvian sulcus (AES) were demonstrated in the cat using the axonal transport methods of autoradiography and horseradish peroxidase. The corticotectal projection arises nearly exclusively from medium-large pyramidal cells in lamina V. One of the densest projecting areas of the AES is the rostral aspect of its superior bank, where a fourth somatotopic representation (SIV) has recently been demonstrated. It terminates in the intermediate and deep laminae of the superior colliculus, where somatic cells are located. The pathway is bilateral but much heavier ipsilaterally than contralaterally. In contrast to the substantial corticotectal projection from SIV and adjacent tissue, there was no unequivocal evidence for a corticotectal projection from traditional somatosensory cortex SI-SIII. This finding, that somatosensory projections to the cat superior colliculus arise from an area outside of SI-SIII, was unexpected on the basis of what is known about visual corticotectal projections. However, it is consistent with the patterns of other cortical projections that terminate in the intermediate and deep laminae of this structure and with the absence of demonstrable corticotectal influences from SI to SIII in this animal. These data are in contrast to demonstrations by other investigators that there is a corticotectal projection from SI cortex in rodents. Apparently there is a fundamental species difference in the organization of descending somatosensory pathways. A corticothalamic projection of the AES was also observed. This descending projection appeared to form a shell of labeled cells and fibers around the ventrobasal complex, but unequivocal terminal labeling within the ventrobasal complex could not be demonstrated. Dense terminal labeling was apparent in the posterior group of thalamic nuclei (PO) where thalamocortical afferents to the AES originate.

Possible anatomical pathways mediating superior colliculus control of pinna movements were determined in the cat using the orthograde autoradiographic tracing method and the retrograde horseradish peroxidase technique. This was done in the following manner. First, the division of the facial nucleus that innervates the pinna muscles was determined by injecting the pinna muscles with HRP and surveying the facial nucleus for retrogradely filled cells. Second, the brainstem regions that project the facial nucleus were identified using the horseradish peroxidase method. Third, the superior colliculus projections to these areas were studied using the autoradiographic tracing method. The results suggest that superior colliculus control of pinna movements is mediated entirely by indirect connections with the facial nucleus and that these connections occur mainly in a paralemniscal zone in the lateral midbrain. Of all the brainstem regions shown by the horseradish peroxidase experiments to project to the facial nucleus only this midbrain paralemniscal zone received a projection from the superior colliculus that was dense and overlapped precisely the region containing facial projecting neurons. Further autoradiographic tracing revealed that the facial nucleus was the primary brainstem target of this paralemniscal zone and that all paralemniscal fibers projecting to the facial nucleus ended in the subdivision that innervates the pinna muscles. Other paralemniscal efferents terminate in the opposite paralemniscal zone. The data suggest that other connections between the superior colliculus and the facial nucleus may occur in the cuneiform nucleus of the midbrain, the region around the oculomotor complex, and the reticular formation dorsal to the superior olive.

The origin, course, and termination of the commissural projection of the superior colliculus were studied using the orthograde and autoradiographic tracing method and the retrograde method utilizing horseradish peroxidase. The complementary and mutually confirming sets of data showed that the commissural fibers interconnect a restricted region of the colliculi. This region includes the strata grisea intermedium and profundum and to a lesser degree the stratum opticum. It extends throughout only the rostral part of the colliculus where it ends abruptly at a level slightly less than half the distance from the anterior border of the deep gray layers. By using the needle used for isotope injection to record multiunit responses to somatic and visual stimuli, direct evidence was obtained that this region falls within that functional area of the colliculus devoted to face representation and central vision. The results also suggested that more commissural fibers arise from lateral than medial parts of this region and that many fibers interconnect corresponding points in the colliculi. In addition to intertectal connections, the commissural projection contains decussating axons which terminate in tegmental structures and within a restricted zone of the central gray matter directly overlying the oculomotor complex. The results are discussed in relation to the possible role the commissural projection plays in the regulation of eye and head movement.

The superior colliculus develops its influence over eye and pinna movements gradually during postnatal maturation. Because superior colliculus cells respond earlier in postnatal life to nonvisual than to visual cues, it seemed likely that efferents involved in pinna movements would develop earlier than those involved in eye movements. In the present study, we examined the projections of the superior colliculus to structures related to the cerebellum and facial nucleus believed to be involved in eye-head coordination and pinna movements. We did this by using the autoradiographic and horseradish peroxidase tracing techniques in 11 kittens, ranging in age from several hours to 14 days postnatal, and in seven adult cats. Even in the youngest animals studied, a dense projection was observed from the superior colliculus to each of the target structures examined. These included the parabigeminal nucleus, paralemniscal zone, dorsolateral pons, and inferior olive. Surprisingly, the only projection observed to undergo any postnatal maturational changes was the one to the paralemniscal zone (involved in the pinna-movement circuit of the superior colliculus), and the changes appeared as a reorganization of the terminal field rather than an increase in the density of transported label. Thus, no evidence was obtained to support our expectation that the superior colliculus efferents involved in orientation of the pinnae would develop earlier than those involved in visual orientation. Instead, each of the efferent projections of the superior colliculus examined in this study appears to be laid down prenatally and becomes adultlike long before functional maturity is reached. Presumably, then, the formation and elaboration of synaptic connections are the protracted postnatal processes that limit the functional properties of these neonatal efferent pathways.

A 10-month-old infant with multiple muscular ventricular septal defects, congestive heart failure, Wolff-Parkinson-White syndrome, and supraventricular tachycardia is presented. The site of ventricular pre-excitation was predicted by analysis of ST-T wave isopotential body surface maps to be in the posterior free wall of the right ventricle. The site was confirmed by epicardial mapping of the ventricles during surgery. The pathyway was cryoblated and the ventricular defects were closed. The patient has been free of pre-excitation and supraventricular tachycardia for over two years since surgery.

The ascending projections of the cuneiform nucleus in the cat were traced by autoradiography in the transverse and sagittal planes following stereotaxically placed injections of (3)H-leucine. The ascending fibers are almost exclusively ipsilateral and enter the diencephalon as a wide radiation. At the mesodiencephalic junction fibers enter the nucleus of the posterior commissure and pretectal nuclei, and others cross in the posterior commissure to distribute to these structures on the contralateral side. More ventrally directed fibers distribute to the fields of Forel and then spread into the posterior hypothalamus and zona incerta. At the caudal level of the ventral thalamic group, the ascending fibers diverge and follow two separate courses. One division of fibers continues forward beneath the ventral thalamic group and distributes to the zpna incerta and dorsal hypothalamic area. It rapidly diminishes in size as it attains more rostral levels where it is found in the bed nuclei of the stria terminalis and the anterior commissure. Other fibers of this division spread laterally to innervate the ventral lateral geniculate nucleus, the lateral hypothalamus, and preoptic area, and still others follow the entire confirmation of the thalamic reticular nucleus. The second division of fiber ascends through midline and intralaminar nuclei, completely encircling the mediodorsal nucleus, which is uninnervated except for a small ventral region. The distribution of this division is heaviest to the paraventricular, parafascicular, and central dorsal nuclei. Neither division is conspicuous rostral to the anterior commissure. No projections to neostriatum or specific thalamic nuclei were evident.

The development of eye movements is a prolonged process which presumably involves the efferents of the superior colliculus. In the present study we sought to determine which, if any, of the colliculus efferents that influence eye movements in adult cats were present in neonatal kittens. The autoradiographic and orthograde horseradish peroxidase tracing methods were employed in kittens ranging from 6 h to 5 weeks of age and in adult cats. Surprisingly, most of the known projections from the superior colliculus which are believed to be involved in eye movements were already present in the youngest animals studied. These included projections to (a) the ventral central gray matter overlying the oculomotor nucleus, and (b) those portions of the pontine and medullary reticular formation which provide excitatory and inhibitory inputs to abducens neurons. Apparently, the pathways over which the superior colliculus influences eye movements are elaborated quite early in life. However, in the predorsal bundle and pontomedullary reticular areas the density of transported label was less in 1-day-old kittens than in older animals. Thus, anatomical as well as functional development of portions of this circuitry appear to require a significant period of postnatal maturation.

To evaluate subsidiary ventricular pacemaker function in 20 children with congenital or surgically induced complete heart block, we measured recovery times following overdrive ventricular pacing. Long-term ECG tape recordings were performed in eight of these children. Ages ranged from 1 month to 17 years. The resting R-R intervals ranged from 595 to 1,740 msec. The ventricles were paced at various cycle lengths of 400 to 1,000 msec with either transvenous electrode catheters or surgically implanted epicardial electrodes. His bundle recordings showed that the site of block did not allow separation of patients with symptoms from those without symptoms. Prolonged recovery times were present in patients with block above the His bundle recording site who had symptoms of syncope or dizziness, as well as in patients who had a wide QRS. However, some asymptomatic patient with heart block above the His bundle recording site also had long recovery times. None of the asymptomatic patients who had ECG tape recordings had paroxysmal tachycardia in more than 300 hours of recordings. However, one symptomatic patient with congenital heart block and a prolonged recovery time had brief episodes of paroxysmal ventricular tachycardia that produced no symptoms at the time of recording. The results suggest that the coexistence of prolonged recovery times and paroxysmal tachycardia may be predisposing factors to the development of symptoms in patients with complete heart block. We believe that further electrophysiologic investigation of this possibility is warranted in patients with heart block.

A comprehensive search for subcortical projections to the cat superior colliculus was conducted using the retrograde horseradish peroxidase (HRP) method. Over 40 different subcortical structures project to the superior colliculus. The more notable among these are grouped under the following categories. Visual structures: ventral lateral geniculate nucleus, parabigeminal nucleus, pretectal area (nucleus of the optic tract, posterior pretectal nucleus, nuclei of the posterior commissure). Auditory structures: inferior colliculus (external and pericentral nuclei), dorsomedial periolivary nucleus, nuclei of the trapezoid body, ventral nucleus of the lateral lemniscus. Somatosensory structures: sensory trigeminal complex (all divisions, but mainly the gamma division of nucleus oralis), dorsal column nuclei (mostly cuneate nucleus), and the lateral cervical nucleus. Catecholamine nuclei: locus coeruleus, raphe dorsalis, and the parabrachial nuclei. Cerebellum: medial, interposed, and lateral nuclei, and the perihypoglossal nuclei. Reticular areas: zona incerta, substantia nigra, midbrain tegmentum, nucleus paragigantocellularis lateralis, and the hypothalamus. Evidence is presented that only the parabigeminal nucleus, the nucleus of the optic tract, and the posterior pretectal nucleus project to the superficial collicular layers (striatum griseum superficiale and stratum opticum), while all other afferents terminate in the deeper layers of the colliculus. Also presented is information concerning the rostrocaudal distribution of some of these afferent connections. These findings stress the multiplicity and diversity of inputs to the deeper collicular layers, and more specifically, identify multiple sources of the physiologically well-known representations of the somatic and auditory modalities in the colliculus.

The descending projections of nucleus cuneiformis in the cat were traced by autoradiography in the transverse and sagittal planes following stereotaxically placed injections of 3H-leucine. Many descending axons are organized into distinct fiber systems, of which the largest and most well-defined crosses directly in the midbrain and descends through the ventromedial tegmentum of the brain stem. This fiber system first terminates profusely in n. reticularis tegmenti pontis and then proceeds through the rhombencephalic tegmentum emitting transversely oriented branches to n. reticularis pontis caudalis and gigantocellularis, the raphe magnus and the facial nucleus...

Cardiac involvement by systemic sarcoidosis is well known, but occurs rarely. It usually manifests as either heart block, heart failure due to direct myocardial involvement, or cor pulmonale. We present the case of a patient with cardiac sarcoidosis who had ventricular tachycardia and congestive heart failure. Although there was other organ system involvement, the cardiac manifestation was the first to become clinically apparent. Therapy consisted of quinidine sulfate to control the arrhythmias and chronic diuretic therapy to control congestive heart failure. Steroid therapy was initially associated with recurrence of the ventricular tachycardia and was discontinued. It was reinstituted 18 months later when other organ system involvement developed with no recurrence of the ventricular tachyarrhythmia. The patient responded well to therapy and is currently doing well. This case is presented to illustrate a somewhat unusual, but nevertheless important, etiology of ventricular tachyarrhythmias. The recognition of underlying sarcoidosis is critical because of the propensity for other organ system involvement by this disease process.

We have carried out a quantitative analysis of the force-interval relationship of the human left ventricle and compared it to previous studies done in both intact subjects as well as isolated muscle. The characteristics of the force-interval relationship of the normal patient resembed those of normal isolated mammalian muscle (except when exposed to high levels of catecholamines). The relationship in group 2 (patients with increased left ventricular dimensions and normal pressure indices) resembled those obtained from isolated muscles from hypertrophied hearts. The relationship from group 3 (patients with increased left ventricular EDDs and depressed pressure indices, two of whom were in clinical heart failure) resumbled those induced in normal muscles exposed to high levels of catecholamines, and those obtained from experimentally induced heart failure. The force-interval relationships of the four patients who fell into the third group were strikingly different from the other groups. This suggests that the force-interval relationship may be useful to describe changes in the inotropic state of the patient's heart.