Genome-wide association studies of smooth pursuit and antisaccade eye movements in psychotic disorders: findings from the B-SNIP study.

Eye movement deviations, particularly deficits of initial sensorimotor processing and sustained pursuit maintenance, and antisaccade inhibition errors, are established intermediate phenotypes for psychotic disorders. We here studied eye movement measures of 849 participants from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) study (schizophrenia N=230, schizoaffective disorder N=155, psychotic bipolar disorder N=206 and healthy controls N=258) as quantitative phenotypes in relation to genetic data, while controlling for genetically derived ancestry measures, age and sex. A mixed-modeling genome-wide association studies approach was used including ~4.4 million genotypes (PsychChip and 1000 Genomes imputation). Across participants, sensorimotor processing at pursuit initiation was significantly associated with a single nucleotide polymorphism in IPO8 (12p11.21, P=8 × 10-11), whereas suggestive associations with sustained pursuit maintenance were identified with SNPs in SH3GL2 (9p22.2, P=3 × 10-8). In participants of predominantly African ancestry, sensorimotor processing was also significantly associated with SNPs in PCDH12 (5q31.3, P=1.6 × 10-10), and suggestive associations were observed with NRSN1 (6p22.3, P=5.4 × 10-8) and LMO7 (13q22.2, P=7.3x10-8), whereas antisaccade error rate was significantly associated with a non-coding region at chromosome 7 (P=6.5 × 10-9). Exploratory pathway analyses revealed associations with nervous system development and function for 40 top genes with sensorimotor processing and pursuit maintenance (P=4.9 × 10-2-9.8 × 10-4). Our findings suggest novel patterns of genetic variation relevant for brain systems subserving eye movement control known to be impaired in psychotic disorders. They include genes involved in nuclear trafficking and gene silencing (IPO8), fast axonal guidance and synaptic specificity (PCDH12), transduction of nerve signals (NRSN1), retinal degeneration (LMO7), synaptic glutamate release (SH3GL2), and broader nervous system development and function.

Unstable angina pectoris: a randomized study of patients treated medically and surgically.

Fifty patients with the clinical syndrome of unstable angina pectoris were evaluated. Twenty-seven were randomized into medical or surgical treatment groups and subsequently followed up. The results of the study reveal that: (1) there is approximately a 16 percent incidence rate of significant left main coronary artery disease in patients with this entity at our institution; (2) 10 percent of patients do not have angiographically significant coronary artery disease; (3) pain relief is better in the surgically treated patients, but the 1 1/2 year survival rate is not significantly different between the groups; (4) 50 percent of the medically treated patients again had the syndrome of unstable angina pectoris in the initial few months of the follow-up period; (5) the operative and late postoperative mortality rate in patients presenting with unstable angina pectoris and left main coronary artery disease in this small group of patients was 43 percent; and (6) four of six patients with this syndrome whose condition was deemed inoperable and who were not randomized died within the subsequent few months.

Traumatic injuries of the diaphragm.

Traumatic injury of the diaphragm is not an infrequent occurrence. With the rise in violence and increasing use of automobiles, more diaphragmetic injuries may be seen, especially in inner-city hospitals. Sixty-six cases from our institution within the last five years were reviewed. Of these there were 41 penetrating injuries and 23 secondary to blunt trauma. Two cases were surgically induced following a difficult decortication for pleuropulmonary tuberculosis. There were ten deaths (15 percent mortality). All deaths were related to the severity of associated injuries. In addition, we analyzed 307 patients with multiple injuries who were dead on arrival and were autopsied by the county medical examiners in a 24-month period. Of the 307 autopsied cases, 16 (5.2 percent) had ruptured diaphragms. Interestingly, all but one of these cases were associated with thoracic aortic injuries. Diagnoses of penetrating diaphragmatic injuries were made during exploration of other injuries. In blunt diaphragmatic rupture, a high index of suspicion in most important in the diagnosis. In 10 of 23 blunt injuries, visceral herniation was noted on initial x-ray films. In four, follow-up films several hours to a day later showed loops of bowel in the chest. In nine cases, there were no apparent visceral herniations on initial films, and in these, the diagnosis was made during surgery for other indications. The surgical approach to diaphragmatic injuries is individualized. Acute left-sided injuries are best approached through the abdomen. Acute right-sided injuries and all chronic injuries should be approached through the chest.

Tuberculous aneurysms of the descending thoracic aorta: report of a case with fatal rupture.

Tuberculous aortic aneurysm is a rare disease entity. The majority of affected patients succumb to perforation and exsanguination. The only chance for survival and cure is by resection and prolonged antituberculosis chemotherapy. Our case illustrates the high risk of rupture of tuberculous aortic aneurysms. Post-mortem examination revealed that the mechanism of aneurysm formation was by direct caseous involvement of the descending thoracic aorta from a juxtaposed left upper lobe parenchymal tuberculous process. Our findings also favor the concept that miliary dissemination (in the presence of tuberculous aortic aneurysm) is the result rather than the cause of the tuberculous aortic process.

Implantable cardioverter defibrillator infection causing constrictive pericarditis.

A case of severe constrictive pericarditis resulting from an indolent Pseudomonas aeruginosa infection of the automatic internal cardiac defibrillator is described. Total explanation of the device was attempted after nine months but was unsuccessful because of dense adhesions under the patch electrodes. The patient subsequently developed clinical and hemodynamic findings of constrictive pericarditis and a second desperate attempt to remove the patches resulted in operative death. Diagnostic modalities for detecting infection of the AICD are reviewed. As soon as there is infection involving any component, the entire lead system and pulse generator should be removed.

Avoidance of esophageal stricture following severe caustic burns by the use of an intraluminal stent.

The high incidence of stricture following conventional therapy for caustic esophageal injuries prompted us to incorporate the esophageal stenting technique of Reyes and colleagues [3, 5, 6] into our protocol for management of such patients. Four adult patients were treated following severe esophageal burns caused by the ingestion of caustic drain cleaner. The severity of the burn was established by early esophagoscopy. Laparotomy and gastrotomy revealed severe but nontransmural gastric burns. The stent was left in place for 21 days. Antibiotics and corticosteroids were also employed. There have been no late strictures. One patient required laryngeal dilation for adhesions and another, tracheal dilation for subglottic stenosis. Contrast roentgenographic studies and esophageal manometry have revealed nearly normal esophageal function up to 20 months following the injury.

Corrosive burns of the esophagus and stomach: a recommendation for an aggressive surgical approach.

During a six-year period ending in December, 1980, 62 patients with a history or clinical evidence of corrosive ingestion were admitted into our institutions. The majority were adults who had attempted suicide. Strong alkali (lye), the most common corrosive agent involved, was ingested by more than half of the patients (39). The remaining 23 patients had ingested weak alkali or nonalkali corrosive agents. Of the 27 patients with severe esophagogastric burns (second- and third-degree), a 43.5% incidence overall, liquid lye was responsible in 21, including 7 of 8 patients with extensive full-thickness esophagogastric necrosis. In sharp contrast, only 1 of the 23 patients who had ingested weak alkali or nonalkali corrosive agents had serious esophagogastric injury. In the first two years of this review, the management approach was the so-called standard one (esophagoscopy, steroids, antibiotics, and dilation) (Group 1). The results were disappointing. In 5 of 9 patients with endoscopic findings of second-degree burns, stricture requiring dilation developed, and all 4 with extensive full-thickness esophagogastric necrosis died. In contrast, during the last four years, with the adoption of a more aggressive surgical approach, that is, early surgical intervention including the use of an intraluminal esophageal stent and radical resection as indicated, missed or delayed diagnosis of full-thickness esophagogastric necrosis with its prohibitive mortality was avoided and the complication of severe esophageal stricture was virtually eliminated (Group 2).(ABSTRACT TRUNCATED AT 250 WORDS)

Pulsatile sternal tumor: report of three cases and a review of the literature.

At our institution, 3 patients with pulsatile sternal tumor have been seen. Although ascending aortic aneurysm frequently is high on the list of differential diagnoses, the likelihood that this tumor is metastatic from either a primary renal or thyroid neoplasm is overwhelming. Of the 15 patients reported, 11 had metastases from a primary renal cell carcinoma, including all 3 of our patients. There were 2 patients with primary myeloma, the only histologically proved primary pulsatile sternal tumor. From the surgical standpoint, only the patient with metastatic renal cell carcinoma has a chance of cure. With the recent report of 2 5-year survivors and our own experience of 1 patient with a long asymptomatic interval following resection of the primary kidney tumor and the secondary sternal metastasis, the attitude of hopelessness for these patients should be challenged and an aggressive approach considered.

Effects of estrogenic (o,p'-DDT; octylphenol) and anti-androgenic (p,p'-DDE) chemicals on indicators of endocrine status in juvenile male summer flounder (Paralichthys dentatus).

Laboratory experiments were conducted with male summer flounder to assess the value of selected measures of endocrine status in fish as indicators of exposure to endocrine-disrupting contaminants. Effects of 1,1,1-trichloro-2-(p-chlorophenyl)-2-(o-chlorophenyl) ethane (o,p'-DDT), octylphenol and 1,1-dichloro-2,2-bis (p-chlorophenyl) ethylene (p,p'-DDE) on hepatosomatic and gonadosomatic indices, plasma steroid hormone levels, vitellogenin production, and gonadal development were evaluated in laboratory-raised, juvenile male summer flounder. Flounder were injected twice with test chemical in a coconut oil carrier. Each chemical was tested at three different concentrations. Estrogenic (o,p'-DDT; octylphenol) and anti-androgenic (p,p'-DDE) chemicals were evaluated alone and in combination (octylphenol plus o,p'-DDT or p,p'-DDE). Additionally, some fish were treated with the natural ligand for the estrogen receptor, 17beta-estradiol. Blood and tissues from different fish in each treatment were sampled 4, 6 and 8 weeks after the first injection. Fish exposed to a combination of o,p'-DDT plus octylphenol were also sampled after 15 weeks. In all cases, responses of fish exposed to a test chemical were compared to control fish sampled at the same time. The following significant differences, relative to controls, were observed in at least one sampling time or at least one concentration of chemical. 17beta-Estradiol-treated flounder exhibited decreased gonadosomatic index (GSI), altered hepatosomatic index (HSI), elevated plasma estradiol, reduced plasma testosterone, and high levels of plasma vitellogenin. Fish treated with o,p'-DDT showed lower GSI, no change in HSI or plasma estradiol, depression of plasma testosterone, and induction of vitellogenesis. Octylphenol treatment resulted in lower GSI, no change in HSI, initially increased plasma estradiol and decreased testosterone, and no vitellogenin production. p,p'-DDE treatment did not significantly alter any indicator relative to controls. In experiments using combinations of chemicals, flounder receiving o,p'-DDT plus octylphenol had lower GSI after 8 weeks and elevated plasma estradiol after 15 weeks exposure. Fish treated with p,p'-DDE plus octylphenol for 8 weeks exhibited a significantly lower GSI. Overall, lower GSI and plasma testosterone levels, relative to controls, were consistent indicators of exposure to estrogenic chemicals in juvenile male flounder. No indicators were found that would identify exposure to the mammalian anti-androgen p,p'-DDE.

Vitellogenin-induced pathology in male summer flounder (Paralichthys dentatus).

Male summer flounder (Paralichthys dentatus) were given two injections (initially and 2 weeks later) of 17beta-estradiol (E2) totaling 0.2 (2 x 0.1), 2.0 (2 x 1.0) or 20.0 (2 x 10.0) mg E2/kg body weight. Blood and tissue samples were collected 4, 6 and 8 weeks after the initial injection in the (2 x 0.1) mg/kg treatment, 4, 6, 8, and 15 weeks after the first injection in the (2 x 1.0) mg/kg treatment and at 4 weeks only in the (2 x 10.0) mg/kg treatment. Five of the 12 fish injected twice with 10.0 mg/kg were moribund before the first sampling period. Circulating levels of vitellogenin (VTG) in the blood of all E2-injected fish from all treatments were comparable with those concentrations found in the blood of wild male carp (Cyprinus carpio) and walleye (Stezostedion vitreum) previously collected near a sewage treatment plant (0.1-10.0 mg VTG/ml plasma). Excessive hyalin material accumulated in the livers, kidneys and testes of the treated fish. A portion of that material was identified as VTG by immunohistochemistry. The accumulation of VTG, and possibly other estrogen-inducible proteins, resulted in hepatocyte hypertrophy, disruption of spermatogenesis, and obstruction or rupture of renal glomeruli.

Involvement of microbial respiratory pathogens in acute interstitial pneumonia in feedlot cattle.

OBJECTIVE: To evaluate viral and bacterial respiratory pathogens and Mycoplasma spp isolated from lung tissues of cattle with acute interstitial pneumonia (AIP) and cattle that had died as a result of other causes. SAMPLE POPULATION: 186 samples of lung tissues collected from cattle housed in 14 feedlots in the western United States. PROCEDURE: Lung tissues were collected during routine postmortem examination and submitted for histologic, microbiologic, and toxicologic examinations. Histologic diagnoses were categorized for AIP, bronchopneumonia (BP), control samples (no evidence of disease), and other disorders. RESULTS: Cattle affected with AIP had been in feedlots for a mean of 1272 days before death, which was longer than cattle with BP and control cattle. Detection of a viral respiratory pathogen (eg, bovine respiratory syncytial virus [BRSV], bovine viral diarrhea virus, bovine herpesvirus 1, or parainfluenza virus 3) was not associated with histologic category of lung tissues. Bovine respiratory syncytial virus was detected in 8.3% of AIP samples and 24.0% of control samples. Histologic category was associated with isolation of an aerobic bacterial agent and Mycoplasma spp. Cattle with BP were at greatest risk for isolation of an aerobic bacterial agent and Mycoplasma spp. CONCLUSIONS AND CLINICAL RELEVANCE: Analysis of these results suggests that AIP in feedlot cattle is not a consequence of infection with BRSV. The increased, risk of isolation of an aerobic bacterial agent from cattle with AIP, compared with control cattle, may indicate a causal role or an opportunistic infection that follows development of AIP.

Association of 3-methyleneindolenine, a toxic metabolite of 3-methylindole, with acute interstitial pneumonia in feedlot cattle.

OBJECTIVE: To compare concentrations of 3-methyleneindolenine (3MEIN) in lung tissues obtained from feedlot cattle that died as a result of acute interstitial pneumonia (AIP) and cattle that died as a result of other causes and to compare blood concentrations of 3MEIN in healthy feedlot cattle and feedlot cattle with AIP. STUDY POPULATION: Blood samples and lung tissues collected from 186 cattle housed in 14 feedlots in the western United States. PROCEDURE: Samples of lung tissues were collected during routine postmortem examination and submitted for histologic, microbiologic, and toxicologic examination. Blood samples were collected from cattle with clinical manifestations of AIP and healthy penmates. Histologic diagnoses were categorized as AIP, bronchopneumonia (BP), control samples, and other disorders. Concentrations of 3MEIN were determined in lung tissues and blood samples, using an ELISA. RESULTS: Concentrations of 3MEIN in lung tissues were significantly greater in AIP and BP samples, compared with control samples. Absorbance per microgram of protein did not differ between BP and AIP samples. Blood concentrations of 3MEIN were significantly greater in cattle with AIP, compared with healthy cattle or cattle with BP. Odds of an animal with AIP being a heifer was 3.1 times greater than the odds of that animal being a steer. CONCLUSIONS AND CLINICAL RELEVANCE: Increased pulmonary production of 3MEIN may be an important etiologic factor in feedlot-associated AIP.