A case report: Hypoxic ischemic encephalopathy & pneumonia in a neonate after SARS-CoV-2 intrauterine transmission.

Severe acute respiratory coronavirus 2 (SARS-CoV-2) is primarily transmitted via respiratory droplet or aerosol route. However, there is mounting evidence for intrauterine transmission. We report on a late preterm infant with suspected intrauterine acquisition of SARS-CoV-2 who experienced birth depression, hypoxic ischemic encephalopathy, multisystem organ involvement, and late onset COVID-19 pneumonia [22].

Evaluation of Clostridium difficile in dogs and the household environment.

Clostridium difficile may be an emerging community-associated pathogen but little is known about its sources of exposure. This study evaluated C. difficile contamination in households and colonization of pets. C. difficile was isolated from 44/836 (5.3%) sites in 26/84 (31%) households. Ribotype 027 was the most common (25%) environmental strain. C. difficile was isolated from 14/139 (10%) dogs. Living with an immunocompromised individual was associated with C. difficile colonization in dogs. All toxigenic strains identified in pets have been isolated from humans in Ontario. C. difficile was isolated concurrently from dogs and the environment in four households, but in all cases canine and environmental ribotypes were different. C. difficile was relatively common in households, suggesting that exposure to this pathogen may be a regular event. There was no evidence that dogs are a significant source of household C. difficile contamination.

Alcohol consumption promotes insulin sensitivity without affecting body fat levels.

OBJECTIVE: Alcohol consumption promotes insulin sensitivity. In obesity, a decrease in body fat levels decreases the risk of developing insulin resistance; therefore, it is possible that alcohol improves insulin sensitivity by negatively affecting body fat. The aim of this study was to determine whether alcohol consumption promotes insulin sensitivity by reducing body fat levels in C57BL/6 male mice. METHODS: We examined the effects of alcohol consumption on insulin sensitivity in male mice with three different body weight (BW) phenotypes. The BWs were induced by feeding the mice a 30% calorie-restricted (CR) regimen, a low-fat (LF) diet and a high-fat (HF) diet. The mice had free access to water or 20% ethanol in the drinking water. To determine the effects of the three different BW phenotypes and of alcohol on glucose regulation and insulin sensitivity, we performed the insulin tolerance test (ITT) and glucose tolerance test (GTT) on the mice. The effects of the diets and alcohol on body composition, percent body fat (% BF), percent lean mass and bone mineral density (BMD) were determined by dual-energy X-ray absorptiometry (DEXA). RESULTS: Data show that mice with the highest body fat levels (HF) were insulin resistant and glucose intolerant. In contrast, mice with the lowest body fat levels (CR) were the most insulin sensitive and cleared the injected endogenous glucose the fastest. Results show that alcohol did not affect GTT in any of the BW phenotypes. However, alcohol consumption promoted insulin sensitivity in mice consuming both the LF and HF diets. Alcohol consumption increased insulin sensitivity without affecting body fat levels, as body fat levels were similar in mice consuming the LF or HF diets and drinking either water or alcohol. CONCLUSIONS: Alcohol consumption promotes insulin sensitivity without affecting body fat levels in mice consuming LF and HF diets.

Interleukin 3 promotes the in vitro proliferation of murine pluripotent hematopoietic stem cells.

Medium conditioned by activated T lymphocytes stimulates the in vitro proliferation of pluripotent hematopoietic stem cells (spleen colony-forming units [CFU-S]) but the factors involved have not been identified. Because the lymphokine interleukin 3 (IL-3) enhances in vitro colony formation by committed hematopoietic progenitor cells, we examined the effect of IL-3 on the in vitro proliferation of CFU-S using an 11-d spleen colony assay. When mouse marrow cells were placed in liquid culture, CFU-S content declined progressively and by 96 h only 13% of the CFU-S remained. By contrast, after 96 h in the presence of 20 U/ml of IL-3, the number of CFU-S were the same as that in the initial inoculum. Although the number of CFU-S eventually declined, they could still be recovered after 264 h of culture. In the absence of IL-3, the number of CFU-S synthesizing DNA was negligible; in its presence, greater than 20% of the CFU-S were in cycle. IL-3 stimulated CFU-S proliferation at a concentration of 0.2 U/ml. The dose-response curve was similar to that observed for other biologic effects of the lymphokine, and as little as 1 h of exposure to IL-3 enhanced the survival of CFU-S in vitro. Treatment of marrow cells with anti-Thy 1.2 antibody and complement before exposure to IL-3 did not inhibit spleen colony formation, but treatment of the cells with anti-Thy 1.2 antibody and complement after exposure to IL-3 reduced CFU-S recovery after 96 h of culture by 45%. The cell composition of day 11 spleen colonies formed by IL-3-treated marrow cells was similar to that of colonies formed by untreated marrow cells. Finally, day 11 CFU-S persisting in the marrow of mice treated with 5-fluorouracil required IL-3 for proliferation in vitro. Taken together, these data indicate that IL-3 promotes the proliferation of CFU-S in vitro, increases the number of CFU-S synthesizing DNA, but does not alter their commitment program, and the target cell population includes CFU-S with self-renewal and marrow-repopulating ability.

Strokes in children due to vertebral artery trauma.

Strokes due to vertebral artery lesions are rare in children. We describe three new patients and compare them with the 16 other patients described in the literature. All of these patients are boys. Traumatic vertebral artery lesion at C1-2 level was the most common cause of stroke, and the prognosis for neurologic recovery was good. We suggest that vertebral artery disease be considered in boys with posterior circulation ischemia.

The spectrum of carcinoma arising in Barrett's esophagus. A clinicopathologic study of 26 patients.

The clinical and pathologic features of carcinoma arising in Barrett's esophagus were studied in resection specimens from 26 patients. White males predominated (73%). A history of symptomatic gastroesophageal reflux was frequently absent, being elicited in only eight of 14 patients (57%) with a carefully obtained history at the time of presentation with carcinoma. Survival was relatively short with a median survival of 23 +/- 5 months, and only three patients had a disease-free survival longer than 2 years. A pathologic spectrum of carcinoma was found: differentiation ranged from well to poorly differentiated in the 20 patients with a single adenocarcinoma; two separate carcinomas were found in four patients; and a spectrum of differentiation in a single tumor was found in the other two cases, one an adenocarcinoid tumor and the other an adenosquamous carcinoma. The tumors were generally far advanced, with extension through the esophageal wall in 23 of 26 cases (88%) and metastases to lymph nodes in 17 of 24 cases (71%). Epithelial dysplasia, including carcinoma in situ in some cases, was found in Barrett's mucosa adjacent to the tumor in all 26 patients. Our findings suggest that a surveillance program for dysplasia in patients known to have Barrett's esophagus is warranted in an attempt to improve the outcome. However, the impact of surveillance on the incidence of Barrett's carcinoma may be lessened by its frequent occurrence in patients with asymptomatic gastroesophageal reflux.

Decreases in endomorphin-2-like immunoreactivity concomitant with chronic pain after nerve injury.

Nerve injury often leads to chronic, sometimes excruciating, pain. The mechanisms contributing to this syndrome include neurochemical plasticity in neurons involved in the earliest stages of pain transmission. Endomorphin-2 (Tyr-Pro-Phe-Phe-NH(2)) is an endogenous morphine-like substance that binds to the mu-opioid receptor with high affinity and selectivity. Endomorphin-2-like immunoreactivity (LI) is present in the superficial layers of the dorsal horn in the spinal cord and in primary afferents, suggesting a role for this peptide in pain transmission. To determine whether spinal endomorphin-2-LI is altered in an animal model of chronic pain, the left sciatic nerve of Swiss Webster and ICR mice was ligated in a modified Seltzer model of nerve injury. Changes in endomorphin-2-LI were assessed by immunocytochemistry at 2, 4 and 14 days after nerve injury. The side of the spinal cord ipsilateral to the nerve injury exhibited a dramatic decrease in endomorphin-2-LI relative to the contralateral side and to control animals. The change was restricted to the medial dorsal horn in the lumbar segments innervated by the sciatic nerve. Substance P-LI showed a small decrease, while calcitonin gene-related peptide-LI was unchanged. Both thermal hyperalgesia, as evidenced by significantly decreased paw withdrawal latencies, and decreased endomorphin-2-LI were observed within 2 days of injury and were most pronounced at 2 weeks after injury. The decrease in endomorphin-2-LI during the development of chronic pain is consistent with the loss of an inhibitory influence on pain transmission. These results provide the first evidence that reduction of an endogenous opioid in primary afferents is associated with injury-induced chronic pain.

Ischemic heart disease secondary to amyloidosis of intramyocardial arteries.

Among 108 patients with cardiac amyloidosis studied at autopsy between 1889 and 1977 there were 5 (4.6 percent) with severe occlusive amyloid deposits in intramyocardial arteries. The hearts of all five patients showed focal subendocardial ischemic injury, and the vessels supplying these areas had either complete or near complete luminal obliteration by amyloid. Clinically, four patients had congestive heart failure; one of these patients also had arrhythmias and one had angina pectoris. Neither the clinical nor the pathologic features of ischemic heart diseases could be attributed to disease of the epicardial coronary arteries. Amyloidosis of the intramyocardial arteries appears to be capable of producing localized areas of ischemic necrosis and may produce intractable congestive heart failure due to multiple areas of ischemic injury.

Schneiderian papillomas: a clinicopathologic study of 67 cases.

The clinical and pathologic features of schneiderian papillomas were studied in 67 patients. There were 40 male and 27 female patients, and the mean age at diagnosis was 49 +/- 17.9 (SD) years. Nasal obstruction or perception of a nasal mass was the most common presenting symptom; mean duration of symptoms was 10.8 +/- 15.8 (SD) months. Almost equal numbers of papillomas had predominantly endophytic (inverted) (n = 32) and predominantly exophytic (fungiform) (n = 30) patterns, and five had mixed patterns. Multiple morphologic variables were evaluated in the initial specimens, including cytologic atypia and number of mitotic figures; there were no statistically significant correlations between these variables and biologic behavior. Of the 39 patients for whom follow-up information was available (mean follow-up period, 38.6 months), six patients (all with predominantly endophytic patterns) had copresented with schneiderian papillomas and carcinomas. The remaining 33 patients initially had only benign schneiderian papillomas. In these 33 patients, recurrences developed in 11 (33 per cent), local invasion in two (6 per cent) (both with inverted papillomas), and epidermoid carcinoma in one (3 per cent) (with an inverted papilloma). Three patients had evidence of disease when last examined, and two patients had died of disease (both after copresentation with schneiderian papillomas and carcinomas). The continued use of the term inverted papilloma (endophytic pattern) as a specific subset of schneiderian papillomas is recommended, as all serious complications, including progression to local invasion, copresentation with carcinoma, and development of carcinoma, were associated with these lesions.

Prevalence and characteristics of Barrett esophagus in patients with adenocarcinoma of the esophagus or esophagogastric junction.

The prevalence and characteristics of Barrett esophagus in patients with adenocarcinoma of the esophagus or esophagogastric junction are uncertain. We studied 61 consecutive esophagogastrectomy specimens with adenocarcinoma, which were subjected to extensive histopathologic examination. Barrett esophagus was found in 64% of the cases (39 of 61), but had been recognized in only 38% of the patients with Barrett-associated carcinoma who had undergone preoperative endoscopy with biopsy (13 of 34). The median extent of Barrett esophagus with adenocarcinoma was 5 cm (range, 1 cm to 12 cm), and distinctive-type ("specialized") Barrett mucosa predominated (35 of 39; 90%). The Barrett adenocarcinomas were centered in the distal esophagus 2 cm +/- 0.3 cm above the esophagogastric junction. The patients with Barrett adenocarcinoma showed a striking predominance of white men (34 of 39; 87%) in contrast to gastric adenocarcinoma cases (21 of 69; 30%) and to Barrett patients without carcinoma or dysplasia (75 of 149; 50%), but similar to patients having adenocarcinoma of the esophagus or esophagogastric junction without demonstrable Barrett esophagus (16 of 22; 73%). Our findings suggest that most adenocarcinomas of the esophagus or esophagogastric junction are Barrett carcinomas, rather than gastric cardiac cancers or other types of esophageal adenocarcinoma; most Barrett adenocarcinomas occur in short segments of Barrett esophagus, which may be difficult to detect at endoscopy; and white men with Barrett esophagus may constitute a clinically identifiable at-risk group suitable for surveillance.

Tailoring the cranio-orbital approach.

The various modifications and variations of the cranio-orbital approach have been recently described; the author uses different modifications according to the location, size and extent of the lesion. Some of the prime indications for these modifications are presented herein.

Use patterns for antipsychotic medications in medicaid patients with schizophrenia.

OBJECTIVE: We investigated the use patterns for antipsychotic medications generated by Medicaid patients with schizophrenia. METHOD: Paid claims data from the California Medicaid program (Medi-Cal) were used to identify 2655 patients with schizophrenia. Data from 1987-1996 were used, during which time Medi-Cal maintained prior authorization restrictions on second generation antipsychotic drugs. Prescription records were used to identify 3 patterns of antipsychotic drug use: no drug therapy for over 1 year; delayed onset of antipsychotic drug therapy; and switches in antipsychotic drugs within 1 year. Multiple logistic regression models were used to identify factors affecting these antipsychotic drug use patterns. RESULTS: Conventional antipsychotic medications account for over 98% of all patient treatment episodes. Over 24% of patients with schizophrenia do not use any antipsychotic medication for periods lasting up to 1 year. Over 24% of treated patients delayed the use of antipsychotic medications at least 30 days. For those patients who did not delay their use of antipsychotic medications, over 47% switched or augmented their initial antipsychotic medication during the first treatment year. Only 11.6% of treated patients achieved 1 year of uninterrupted antipsychotic drug therapy. The mean duration of uninterrupted therapy was 142 days. DISCUSSION: Antipsychotic drug use patterns suggest that conventional antipsychotic medications do not meet the therapeutic needs of patients with schizophrenia.

The relationship between columnar epithelial dysplasia and invasive adenocarcinoma arising in Barrett's esophagus.

The authors assessed the relationship between dysplasia in Barrett's esophagus and invasive adenocarcinoma in a study of both endoscopic biopsy specimens and esophagectomy specimens. They reviewed the pathologic findings and clinical follow-up of 14 patients with dysplasia in Barrett's mucosa in endoscopic biopsy specimens. They also studied systematically the histopathologic features of the Barrett's mucosa in 43 esophagectomy specimens resected for Barrett's carcinoma. In the biopsy specimens, dysplasia occurred in distinctive-type Barrett's mucosa of 13 patients (93%) but in cardiac-type mucosa of only 3 (21%). Six patients had high-grade dysplasia; five underwent esophagectomy and three of these were found to have superficially invasive adenocarcinoma. The other patient with high-grade dysplasia as well as eight patients with intermediate- or low-grade dysplasia are not known to have carcinoma on available follow-up. In the study of resection specimens, high-grade dysplasia was strongly associated with adjoining invasive adenocarcinoma, because 84% of areas with invasion had high-grade dysplasia and 92% of areas with high-grade dysplasia showed invasion. The authors' findings suggest that the dysplasia-carcinoma sequence most commonly occurs in Barrett's mucosa of the distinctive type; high-grade dysplasia in Barrett's mucosa is a marker indicating high probability of invasive carcinoma; the presence of high-grade dysplasia in biopsy specimens of Barrett's mucosa is an indication for esophagectomy in suitable surgical candidates.

An EPR investigation of surfactant action on bacterial membranes.

The effects of the surfactants, alcohol ethoxylate, amine ethoxylate, amine oxide and SDS on cell membranes were investigated using the lipid soluble spin label 5-doxyl stearic acid (5-DS). Electron paramagnetic resonance (EPR) spectroscopy revealed that the action of the surfactants was to significantly increase membrane fluidity of Proteus mirabilis, Staphylococcus aureus and Saccharomyces cerevisiae. The action of these surfactants as biocides was investigated and found to be dependent on the type of organism tested. There was, however, no direct correlation between enhanced membrane fluidity observed due to the action of the surfactants and biocidal activity. Data presented suggest that perturbing the fluidity of the cytoplasmic membrane is not immediately responsible for cell death.

Prospective, randomized trial of autotransfusion after routine cardiac operations.

To study the effectiveness of autotransfusion of shed mediastinal blood in decreasing the need for homologous blood transfusion in the routine cardiac surgical patient, we prospectively randomized 35 consecutive patients into two groups. The experimental group (n = 18) received autotransfusion for 12 hours after completion of the operative procedure. The control group (n = 17) was treated with standard chest drainage and fluid replacement. Both groups received homologous blood transfusion when the hemoglobin level fell to less than 8.0 g/dL. Student's t test, chi 2 analysis, and multivariate logistic regression analysis were used where appropriate. Packed red blood cells were required postoperatively in 6 of the 17 control and 6 of the 18 autotransfusion patients (p = not significant). Postoperative colloid fluid replacement (excluding autotransfusion fluid) in the autotransfusion group (333 +/- 78 mL; 95% confidence bounds, 168 to 498 mL) was less than in the control group (615 +/- 114 mL; 95% confidence bounds, 372 to 857 mL; p = 0.048). Total homologous blood product exposure tended to be higher in autotransfusion patients (83%) than in control patients (47%) (p = 0.057). Fibrin split products were elevated only in the serum of the autotransfusion patients (p < 0.002). No transfusion-related complications were apparent in either group. Although the sample size is small, autotransfusion of shed mediastinal blood does not appear to decrease the need for homologous blood transfusion in the routine cardiac surgical patient.

The presence of the 21-hydroxylase deficiency carrier status in hirsute women: phenotype-genotype correlations.

OBJECTIVE: To determine the role of heterozygosity for mutations in the 21-hydroxylase gene (CYP21) in the pathogenesis of hyperandrogenism. DESIGN: Controlled clinical study. SETTING: Tertiary care institutional hospital. PATIENT(S): Forty hirsute women and 13 healthy control women. INTERVENTION(S): The source of androgen excess was determined by the changes in serum testosterone levels in response to a single 3.75-mg i.m. dose of triptorelin. MAIN OUTCOME MEASURE(S): CYP21 molecular genetic analysis and serum 17-hydroxyprogesterone levels. RESULT(S): Eight patients and one control were heterozygous carriers of CYP21 mutations. Two patients with adrenal hyperandrogenism and one patient with ovarian hyperandrogenism, who carried the V281L mutation had an increased ACTH-stimulated 17-hydroxyprogesterone level (>4.1 ng/mL) that persisted during gonadal suppression. Another patient with adrenal hyperandrogenism carried the V281L mutation, and her ACTH-stimulated 17-hydroxyprogesterone level was elevated only during gonadal suppression. Four patients (three with idiopathic hirsutism, one with ovarian hyperandrogenism) and one control were carriers of CYP21 mutations typically associated with classic congenital adrenal hyperplasia but had normal basal and ACTH-stimulated 17-hydroxyprogesterone levels. Nine patients without CYP21 mutations had increased ACTH-stimulated 17-hydroxyprogesterone levels; these decreased to normal in six of the patients during gonadal suppression. CONCLUSION(S): The response of serum 17-hydroxyprogesterone to ACTH does not predict CYP21 carrier status. No clear concordance was found between the CYP21 genotype and the functional origin of androgen excess.

Familial hypophosphatemic rickets causing ocular calcification and optic canal narrowing.

In a case of familial hypophosphatemic rickets, marked bone thickening caused narrowing of the optic canals, resulting in bilateral optic atrophy. The case also showed metastatic calcification in the walls of both globes.

Central nervous system cryptococcosis: parenchymal calcification and large gelatinous pseudocysts.

In an 11-year-old immunocompetent girl with protracted cryptococcal infection of the central nervous system, CT showed multiple areas of parenchymal calcification. MR imaging showed large gelatinous pseudocysts around the brain stem. These imaging features and the child's age are unusual for intracranial cryptococcosis.

Meningeal myelomatosis: CT and MR appearances.

Meningeal myelomatosis is a rare feature of multiple myeloma. We report a case of IgG-kappa myeloma presenting as bilateral intracranial extraaxial masses.

Neuroimaging of disseminated germ cell neoplasms.

The purpose of this study was to determine the role of neuroimaging in the management of patients with metastatic germ cell tumors. Retrospective evaluation of 299 patients treated in 1986 and 1987 for initial presentation or recurrence of testicular, retroperitoneal, and mediastinal germ cell tumors was performed to determine indications for neuroimaging, frequency and site of CNS metastases, and occurrence of other CNS abnormalities. Sixty-six patients required CNS imaging with myelography, CT, or MR. Studies were normal in 24 patients. Twenty patients had CNS metastases including 11 with intracranial metastases, eight with spine lesions, and one with both brain and spine involvement. Sixteen had cerebral or cerebellar atrophy of unclear origin and functional significance. Two patients had ventriculomegaly without symptoms of hydrocephalus. Four patients had questionable lesions that were never confirmed. None of the 25 asymptomatic patients with elevated serum tumor markers had brain metastases. Fifteen of 17 patients with focal neurologic deficits and three of six patients with seizures had CNS metastases. CNS imaging to detect germ cell tumor metastases is most useful in the presence of neurologic deficits or seizures but is not useful in patients with unexplained elevation of serum tumor markers in the absence of neurologic deficits.