An acute, ulcerative, sarcoidal tattoo reaction following SARS-CoV-2 mRNA-1273 vaccination.

Two weeks after her first dose of the SARS-CoV-2 mRNA-1273 (Moderna) vaccine, a 38-year-old woman developed acute-onset pain and ulceration within a tattoo on the distal left leg. Progressive ulceration was noted approximately one week following her second dose of the vaccine. A biopsy revealed sarcoidal granulomas and a dense neutrophilic infiltrate. Ultimately, the final diagnosis of what we have termed a "sarcoidal reaction with a Sweet-like phenomenon" was made; the patient experienced a reduction in pain and re-epithelialization of the ulcers with two weeks of the use of topical clobetasol 0.05% cream twice daily.

High incidence of tuberculosis among HIV-infected infants: evidence from a South African population-based study highlights the need for improved tuberculosis control strategies.

BACKGROUND: There are limited population-based estimates of tuberculosis incidence among human immunodeficiency virus (HIV)-infected and HIV-uninfected infants aged < or =12 months. We aimed to estimate the population-based incidence of culture-confirmed tuberculosis among HIV-infected and HIV-uninfected infants in the Western Cape Province, South Africa. METHODS: The incidences of pulmonary, extrapulmonary, and disseminated tuberculosis were estimated over a 3-year period (2004-2006) with use of prospective representative hospital surveillance data of the annual number of culture-confirmed tuberculosis cases among infants. The total number of HIV-infected and HIV-uninfected infants was calculated using population-based estimates of the total number of live infants and the annual maternal HIV prevalence and vertical HIV transmission rates. RESULTS: There were 245 infants with culture-confirmed tuberculosis. The overall incidences of tuberculosis were 1596 cases per 100,000 population among HIV-infected infants (95% confidence interval [CI], 1151-2132 cases per 100,000 population) and 65.9 cases per 100,000 population among HIV-uninfected infants (95% CI, 56-75 cases per 100,000 population). The relative risk of culture-confirmed tuberculosis among HIV-infected infants was 24.2 (95% CI, 17-34). The incidences of disseminated tuberculosis were 240.9 cases per 100,000 population (95% CI, 89-433 cases per 100,000 population) among HIV-infected infants and 14.1 cases per 100,000 population (95% CI, 10-18 cases per 100,000 population) among HIV-uninfected infants (relative risk, 17.1; 95% CI, 6-34). CONCLUSIONS: This study indicates the magnitude of the tuberculosis disease burden among HIV-infected infants and provides population-based comparative incidence rates of tuberculosis among HIV-infected infants. This high risk of tuberculosis among HIV-infected infants is of great concern and may be attributable to an increased risk of tuberculosis exposure, increased immune-mediated tuberculosis susceptibility, and/or possible limited protective effect of bacille Calmette-Guérin vaccination. Improved tuberculosis control strategies, including maternal tuberculosis screening, contact tracing of tuberculosis-exposed infants coupled with preventive chemotherapy, and effective vaccine strategies, are needed for infants in settings where HIV infection and tuberculosis are highly endemic.

Predator odor produces anxiety-like behavioral phenotype in planarians that is counteracted by fluoxetine.

Avoidant behavior is a characteristic feature post-traumatic stress disorder (PTSD) and is modeled in mammals with predator odor. Light avoidance is a hallmark behavioral reaction in planarians. We hypothesized that planarians exposed to frog extract would display enhanced light avoidance that is prevented by fluoxetine. Enhanced light avoidance (i.e., less time spent in light compartment of a dish split into light and dark sides) after a 30-min frog extract exposure (0.0001-0.01%) manifested 15 min post-exposure, persisted for at least 24 h, and was counteracted by fluoxetine (10 µM). These results suggest conservation of an anxiety-like behavioral phenotype.

Effects of microbead surface chemistry on DNA loading and hybridization efficiency.

Polymer microbeads are witnessing renewed interest for performing biomolecule recognition assays with distinct advantages over planar microarray technology. In this study, DNA hybridization assays are performed on the surfaces of 1-microm-diameter, synthetically modified polystyrene microbeads. The microbead surfaces contain varying amounts of poly(acrylic acid) as a source of carboxylate groups to which a DNA capture strand may bind. Through a series of controlled experiments in which the microbead carboxylate density and DNA:surface area ratios are systematically altered, we find that the density of carboxylate groups on the microbead surface may be the most important parameter affecting not only the total number of DNA strands that may bind to the microbead surface but, surprisingly, also the efficiency of DNA hybridization with complementary strands. These studies are aimed directly at understanding the physical interactions between DNA strands and an anionic microbead surface.

Restricted patterns of CD44 variant exon expression in human papillary thyroid carcinoma.

CD44 is a polymorphic family of cell surface proteoglycans and glycoproteins implicated in cell-cell and cell-matrix adhesion interactions, cell migration, and tumor metastasis. CD44 exists as a standard form and as multiple isoforms arising from alternative splicing of variant exons (termed v1-v10) encoding parts of the extracellular domain. We demonstrated previously that papillary thyroid carcinomas exhibit aberrant patterns of alternative CD44 mRNA splicing (G. Ermak et al., Cancer Res., 55: 4594-4598, 1995). In the present report, we use reverse transcription-PCR using a new high-performance polymerase formulation (Ex Taq; TaKaRa Shuzo Co., Ltd., Otsu, Japan) , followed by Southern hybridization, and demonstrate that alternative exon usage in papillary thyroid carcinomas is restricted primarily to exons v6, v7, v8, v9, and v10, with weak expression of v3. Expression of v8 is tightly linked to v9 and closely related to v10 expression. Also, v6 and v7 expression are closely related. Papillary thyroid cancers exhibit a marked increase in specific mRNA species containing combinations of exons v6 to v10. Several isoforms found in papillary cancers are not detectable in histologically normal tissue derived from the corresponding contralateral thyroid lobes. Examples include a 750-bp v6- and v7-containing PCR product and a 650-bp v8- and v9- containing PCR product. Finally, a novel 530-bp PCR product was discovered and shown to contain a subsegment from exon 4 joined to a subsegment of exon 13 (v8), followed by the complete sequence of exons 14 (v9) and 15 (v10). This novel isoform was present in both the papillary cancers and contralateral tissues. In conclusion, papillary thyroid cancers exhibit specific patterns of aberrant alternative CD44 splicing, distinguishing them from histologically normal thyroid tissue.

Deregulated alternative splicing of CD44 messenger RNA transcripts in neoplastic and nonneoplastic lesions of the human thyroid.

CD44 is a polymorphic family of immunologically related cell surface proteoglycans and glycoproteins implicated in cell-cell and cell-matrix adhesion interactions, lymphocyte activation and homing, cell migration, and tumor metastasis. CD44 exists as a standard form and as multiple isoforms, each generated by alternative splicing of up to 10 variant exons (termed v1-v10) encoding parts of the extracellular domain. Using semiquantitative reverse transcriptase-PCR and Southern hybridization, alternative CD44 mRNA splicing was examined in 10 papillary thyroid carcinomas, 8 nodular goiters, 9 adenomas, 2 cases of thyroiditis, and 3 histologically normal thyroid controls. The amount of input cDNA for the CD44 PCRs was standardized against an internal control gene (glyceraldehyde phosphate dehydrogenase). Four papillary carcinomas showed significant overexpression of CD44 transcripts migrating between 750 and 1000 bp. These cases demonstrated reduced levels of the 482-bp standard isoform transcript. In six papillary cancers, we found a prominent v6-containing isoform at 750 bp that was present in only trace amounts in normal thyroid tissue. It is of interest that similar findings were seen in the majority of the goiters and adenomas but not in the cases of thyroiditis. These results show that deregulation of alternative CD44 splicing is a common feature of disordered thyroid follicular cell growth, both in neoplastic and nonneoplastic lesions. The data imply an important role for CD44, including CD44v6, in the pathogenesis of various thyroid lesions.

The influence of maternal nutrition on expression of genes responsible for adipogenesis and myogenesis in the bovine fetus.

The objective of this study was to determine whether altered maternal energy supply during mid-gestation results in differences in muscle histology or genes regulating fetal adipose and muscle development. In total, 22 Angus cross-bred heifers (BW=527.73±8.3 kg) were assigned randomly to the three dietary treatments providing 146% (HIGH; n=7), 87% (INT; n=7) or 72% (LOW; n=8) of the energy requirements for heifers from day 85 to day 180 of gestation. Fetuses were removed via cesarean section at day 180 of gestation and longissimus muscle (LM) and subcutaneous fat were collected and prepared for analysis of gene expression. Samples from the LM and semitendinosus (ST) were evaluated for muscle fiber diameter, area and number. The right hind limb was dissected and analyzed to determine compositional analysis. Fetal growth and muscle histology characteristics of the LM and ST were similar among treatments. Preadipocyte factor-1 expression was up-regulated in fetal LM (P<0.05) of HIGH fetuses as compared with INT, whereas LOW fetuses showed increased CCAAT/enhancer-binding protein-ß (C/EBP-ß) expression in LM as compared with INT (P<0.05). Peroxisome proliferator-activated receptor γand C/EBP-α did not differ as a result of dietary treatment in LM or subcutaneous fat samples. There was a tendency for increased expression of fatty acid synthase in LM of LOW fetuses as compared with INT (P<0.10). Myogenin was more highly expressed (P<0.05) in LM of the LOW fetuses, whereas µ-calpain expression was increased in the HIGH treatment compared with INT. A tendency for increased expression of IGF-II was observed for both LOW and HIGH fetuses compared with INT (P<0.10). Expression of stearoyl-CoA desaturase, myoblast determination protein 1, myogenic factor 5, myogenic regulatory factor-4, m-calpain, calpastatin, IGF-I and myostatin was similar between treatments. Collectively, these results suggest that fetal growth characteristics are not affected by the level of maternal nutritional manipulation imposed in this study during mid-gestation. However, differences in expression of fetal genes regulating adipose and muscle tissue growth and development could lead to differences in postnatal composition and warrants further investigation.

Novel CD44 messenger RNA isoforms in human thyroid and breast tissues feature unusual sequence rearrangements.

CD44 is a family of cell surface proteins implicated in adhesion interactions and tumor metastasis. Multiple CD44 mRNA isoforms arise from alternative splicing of variant exons (termed v1-v10). We recently discovered a novel CD44 mRNA isoform in human papillary thyroid cancers featuring a junction between subsegments of exons 4 and 13 (v8). The sequence ACAG was repeated at both the donor and acceptor sites in the genomic DNA (G. Ermak et al., Cancer Res., 56: 1037-1042, 1996). We used reverse transcription-PCR to characterize expression of this isoform in a panel of thyroid lesions. In addition, we assayed three cryopreserved human breast cancers and two samples of normal breast tissue (from female subjects who had undergone cosmetic mammoplasty) to determine whether a similar isoform is present in breast carcinomas. Levels of the novel isoform were up-regulated in 88% of the goiters, adenomas, and papillary cancers, but were undetectable in cases of thyroiditis and absent or low-level in four samples of normal thyroid tissue. The three breast cancers each yielded a 546-bp PCR product that was not detected in normal breast tissue. The PCR product from one of the breast cancers was cloned, and sequence analysis revealed a novel mRNA isoform featuring a junction between exon 3 and an internal site within exon 13 (v8). The sequence GCTTCAG was repeated at both the donor and acceptor sites in the genomic DNA. These results show that human thyroid and breast tissues contain novel CD44 mRNA isoforms featuring unusual rearrangements at repeated sequences. Further studies are warranted to determine whether the expression of this class of isoforms correlates with growth status.

Effect of dihydroergotamine on +Gz acceleration tolerance.

Dihydroergotamine is a potent vasoconstrictor of the venous capacitance vessels and has been shown to decrease blood pooling in patients with orthostatic hypotension. Acceleration acting on the long axis of the body (+Gz) pools blood into the lower body of the subject. Nine healthy men received an injection of 1 mg dihydroergotamine and 1 ml of saline intramuscularly in a randomised, double blind fashion, and had their Gz acceleration tolerances measured. Dihydroergotamine significantly increased Gz tolerance by 0.24 G and narrowed the difference between the maximum heart rate during the acceleration epoch and resting baseline by 10%. The drug had no effect on blood pressure and heart rate when the subjects changed from the supine to standing position. The increase in Gz tolerance was not sufficient for operational use.

Redo carotid endarterectomy versus primary carotid endarterectomy.

BACKGROUND AND PURPOSE: Several authorities have recently advocated carotid stenting for recurrent carotid stenosis because of the perception that redo surgery has a higher complication rate than primary carotid endarterectomy (CEA). This study compares the early and late results of reoperations versus primary CEA. METHODS: All reoperations for recurrent carotid stenosis performed during a recent 7-year period by a single vascular surgeon were compared with primary CEA. Because all redo CEAs were done with polytetrafluoroethylene (PTFE) or vein patch closure, we only analyzed those primary CEAs that used the same patch closures. A Kaplan-Meier life-table analysis was used to estimate stroke-free survival rates and freedom from >/=50% recurrent stenosis. RESULTS: Of 547 primary CEAs, 265 had PTFE or saphenous vein patch closure, and 124 reoperations had PTFE or vein patch closure during the same period. Both groups had similar demographic characteristics. The indications for reoperation and primary CEA were symptomatic stenosis in 78% and 58% of cases and asymptomatic >/=80% stenosis in 22% and 42% of cases, respectively (P<0.001). The 30-day perioperative stroke and transient ischemic attack rates for reoperation and primary CEA were 4.8% versus 0.8% (P=0.015) and 4% versus 1.1%, respectively, with no perioperative deaths in either group. Cranial nerve injury was noted in 17% of reoperation patients versus 5.3% of primary CEA patients; however, most of these injuries were transient (P<0.001). Mean hospital stay was 1.8 days for reoperation versus 1.6 days for primary CEA. Cumulative rates of stroke-free survival and freedom from >/=50% recurrent stenosis for reoperation and primary CEA at 1, 3, and 5 years were 96%, 91%, and 82% and 98%, 96%, and 95% versus 94%, 92%, and 91% and 98%, 96%, and 96%, respectively (no significant differences). CONCLUSIONS: Reoperation carries higher perioperative stroke and cranial nerve injury rates than primary CEA. However, reoperations are durable and have stroke-free survival rates that are similar to primary CEA. These considerations should be kept in mind when carotid stenting is recommended instead of reoperation.

Observations on bronchiolo-alveolar carcinomas with special emphasis on localized lesions. A clinicopathological, ultrastructural, and immunohistochemical study of 11 cases.

Pathological and clinical features in early localized mucinous and nonmucinous bronchiolo-alveolar carcinomas (BAC) have not been adequately compared. In an attempt to characterize such lesions, we studied the clinicopathological, ultrastructural, and immunohistochemical features of three mucinous and eight nonmucinous BAC (four Clara cell, four Type II pneumocyte) along with one sheep pulmonary carcinoma (SPC). Tumor border, associated fibroplasia, tumor cell incohesion, lymphocytic infiltrate, T-lymphocytes, Langerhans cells (LC), and Leu-M1 and OC 125 immunoreactivity were evaluated. Localized tumors of both types had a similarly favorable prognosis, even when the tumor size was greater than 3 cm or showed more complex histology. Type II pneumocyte carcinomas with tumor cell disassociation and desquamation or a pseudomesotheliomatous phenotype did poorly. Clara cell and type II carcinomas elicited an LC and T-lymphocyte immune response. LC and T-lymphocytes were absent in mucinous BAC and SPC. All of the three mucinous and three of the seven nonmucinous BAC were Leu-M1 negative, indicating that Leu-M1 may not distinguish between BAC and mesothelioma, especially in a small biopsy specimen. Tumors with absent or slight Leu-M1 immunoreactivity had a favorable outcome irrespective of cell type and presence or absence of LC. Inasmuch as OC 125 was negative in all cases of BAC, OC 125 may be a useful adjunct in the immunodiagnosis of mesothelioma. Our investigation supports the view that two different groups of tumors are assembled under the single nosologic entity of BAC: one, mucinous, which grows along an unaltered pulmonary alveolar framework and elicits a B-lymphocytic response, and the other, nonmucinous, which induces desmoplasia and elicits an LC and T-lymphocytic response. Only mucinous BAC represent a biologic entity distinct from conventional pulmonary adenocarcinomas.

Pseudomyxoma ovariilike posttherapeutic alteration in prostatic adenocarcinoma: a distinctive pattern in patients receiving neoadjuvant androgen ablation therapy.

Neoadjuvant combination endocrine therapy that uses leuprolide and flutamide may result in various histologic changes in nontumoral and cancerous prostatic tissues. Posttreatment pseudomyxoma ovariilike change in prostatic adenocarcinoma is a distinctive alteration that may be the only evidence of regressed tumor and can be potentially confused with mucinous carcinoma. We studied 53 clinically localized prostatic adenocarcinomas after 3 to 5 months of treatment with leuprolide and flutamide. Alterations in prostatic adenocarcinoma in posttreatment radical prostatectomy specimens were assessed and compared with pretreatment needle biopsies. All radical prostatectomy specimens exhibited previously well-characterized therapy-associated changes in benign and malignant elements. Thirteen (20%) cases exhibited a distinctive alteration not seen in pretreatment needle biopsies that consisted of minute to large pools of extravasated secretions that resembled pseudomyxoma ovarii and that dissected through prostatic stroma with an infiltrative appearance when viewed at low power. Associated recognizable tumor was present in 10 of 13 (77%) of these cases. Secretions were basophilic in routine sections and contained occasional degenerated cells. Rare pancytokeratin positive cells were seen at the secretion/stroma interface with uniformly negative staining for the high molecular weight keratin 34 beta E-12. The secretions were periodic acid-Schiff positive after diastase digestion and were mucicarminophilic and reactive with Alcian blue at a pH of 2.5. These foci comprised < 5% of the tumor in 5 cases and 5-40% in 5 cases. In 3 cases, 1-2 foci < 1.0 mm exhibited the pseudomyxoma ovariilike changes and were the only evidence of treated tumor. There was no correlation between the presence of pseudomyxomalike change and dose/duration of neoadjuvant therapy, postprostatectomy clinical follow-up, original or final Gleason pattern/score, or pathologic stage. Pseudomyxoma ovariilike change consists of extravasated acid mucin, lacks prostatic basal cells, often occurs in intimate association with residual prostatic adenocarcinoma in posttreatment radical prostatectomy specimens, and probably represents tumor regression as a result of tumor cell attrition secondary to androgen ablation.

Infantile myofibromatosis. Evidence for an autosomal-dominant disorder.

Infantile myofibromatosis is a distinct clinicalpathologic entity occurring primarily in neonates and infants either as a single nodular lesion or as a multicentric form. We have recently studied two cases of this disorder in neonates, and a third involving the father of one of these infants, all documented by biopsy. Evidence in support of an autosomal-dominant mode of inheritance for infantile myofibromatosis and of its potential to recur after a long period of quiescence is presented.

Needle biopsy DNA ploidy status predicts grade shifting in prostate cancer.

DNA ploidy analysis of prostate needle biopsy specimens was performed to determine whether ploidy status could predict tumor grade shifting at radical prostatectomy. The paired needle biopsy and radical prostatectomy specimens from 111 randomly selected men with prostate cancer were obtained from the surgical pathology files of the Albany Medical Center Hospital. The original tumor grades were assigned by a staff of 12 surgical pathologists according to the Gleason system. Tumors with original Gleason scores < or = 6 were classified as low grade, and tumors with scores of > or = 7 were considered high grade. DNA ploidy analysis was performed on the needle biopsy specimens using the CAS 200 image analyzer (Becton Dickinson Immunocytometry Systems, Mountain View, CA, USA) on Feulgen stained 5-microm tissue sections. There were 88 diploid and 23 nondiploid cases. Thirty-eight of 111 (34%) of cases had grade shifting from needle biopsy to radical prostatectomy specimens. Of 89 low-grade needle biopsy cases, 28 (31%) were upgraded at radical prostatectomy. Of 22 high-grade needle biopsy cases, 10 (45%) were downgraded to low grade at radical prostatectomy. Of the 28 low-grade needle biopsy specimens that were upgraded at radical prostatectomy, 19 (68%) featured an aneuploid histogram and 9 (32%) were diploid. Nineteen of 28 (68%) of aneuploid low-grade tumors on needle biopsy became high-grade at radical prostatectomy. Nine of 10 (90%) diploid high-grade tumors at needle biopsy became low-grade at radical prostatectomy. Of the 38 cases in which ploidy and grade were incongruous, 28 (74%) had grade shifting. In a multivariate regression analysis, a high-grade Gleason score on radical prostatectomy specimens correlated significantly with needle biopsy ploidy (p = 0.0001) but not with needle biopsy grade (p = 0.15). The sensitivity of the needle biopsy grade in the detection of high-grade tumors on radical prostatectomy was 30%, and the specificity was 86%. The sensitivity of ploidy status in the prediction of high grade at radical prostatectomy was 78%, and the specificity was 96%. With a prostate-specific antigen (PSA) level of >0.4 ng/ml as the indicator of post-radical prostatectomy disease recurrence on a subset of 106 patients, on univariate analysis, disease recurrence was predicted by needle biopsy ploidy (p = 0.001) and radical prostatectomy grade (p = 0.04) but not by needle biopsy grade (p = 0.39). On multivariate analysis, needle biopsy DNA ploidy status independently predicted disease recurrence (p = 0.002), whereas needle biopsy and prostatectomy grade did not. These results indicate that DNA ploidy analysis of needle biopsy specimens of prostate cancer predicts grade shifting, that it is a more sensitive and specific indicator of final tumor grade at radical prostatectomy than is the original needle biopsy grade, and that ploidy status independently predicts postoperative disease recurrence.

Association of p53 immunoreactivity with high gleason tumor grade in prostatic adenocarcinoma.

To determine whether p53 immunoreactivity correlates with the Gleason tumor grade in primary adenocarcinoma of the prostate we analyzed 107 consecutive surgical specimens (78 radical prostatectomies and 29 transurethral resections). A hematoxylin-eosin-stained slide from a representative block of each tumor was examined, and primary and secondary Gleason scores were assigned in each case. Additional paraffin sections from the same block were stained immunohistochemically for p53 expression using the monoclonal antibody clone DO-1, a mouse IgG2a directed against a denaturation-resistant epitope of p53. Four of 54 (7.4%) low-grade tumors (combined Gleason score of 6 and below) and 11 of 53 (20.8%) high-grade tumors (combined Gleason score of 7 and above) revealed strong nuclear positivity for p53. When evaluated using only the primary Gleason score, none of 23 (0%) Gleason grade 2 tumors and 15 of 84 (17.9%) Gleason grade 3 or higher tumors were positive. These data demonstrate a positive association between p53 immunoreactivity and higher Gleason grade tumors (P = .04 for the combined score, P = .02 for primary score only). In addition, we noted occasional p53-positive nuclei in basal cells of benign glandular acini in regions flanking tumor. Focally positive nuclear staining also was demonstrated in basal cells from nine of 25 prostate glands exhibiting benign prostatic hyperplasia with no tumor. These results suggest that p53 overexpression might be associated with the known proliferative capacity of basal cells in benign hyperplastic prostate glands, and that mutations of p53 might play a role in the pathogenesis of a subset of high-grade prostate adenocarcinomas.

Safety, tolerance and pharmacokinetics of a humanized monoclonal antibody to respiratory syncytial virus in premature infants and infants with bronchopulmonary dysplasia. MEDI-493 Study Group.

BACKGROUND: Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection in infants. MEDI-493 (palivizumab) is a humanized monoclonal antibody to the fusion protein of RSV and is active in animal models for prevention of pulmonary RSV replication. OBJECTIVE: To describe the safety, tolerance, immunogenicity and pharmacokinetics of repeat intravenous doses of MEDI-493 in premature infants or infants with bronchopulmonary dysplasia. DESIGN: Phase I/II multicenter, randomized, double blind, placebo-controlled, dose escalation trial. PATIENT POPULATION: Infants born prematurely (< or = 35 weeks of gestation) who were < or = 6 months of age and infants with bronchopulmonary dysplasia who were < or = 24 months of age were eligible for study participation. STUDY AGENTS: Participants received 3, 10 or 15 mg/kg MEDI-493 or 0.9% saline intravenously every 30 days for up to five doses. RESULTS: MEDI-493 was safe and well-tolerated and did not induce a specific anti-MEDI-493 response. The mean half-life of 20 days was comparable with that of other immunoglobulin G preparations. Mean trough serum concentrations 30 days after Infusion 1 were 6.8, 36.1 and 60.6 microg/ml for the 3-, 10- and 15-mg/kg dose groups, respectively. After Infusion 2 the trough concentrations were 11.9, 45.2 and 70.7 microg/ml. After subsequent doses the mean trough values ranged from 14 to 18 microg/ml in those given 3 mg/kg and were > 40 microg/ml for patients who received 10 or 15 mg/kg MEDI-493 (46 to 72 microg/ml and 88 to 96 microg/ml, respectively). CONCLUSIONS: MEDI-493 was safe and well-tolerated in this high risk pediatric population. Mean serum concentrations of MEDI-493 that have been shown to produce a 2-log reduction in pulmonary RSV titer in cotton rats were maintained when 10 or 15 mg/kg MEDI-493 was given every 30 days to pediatric patients at high risk for serious RSV disease. Monthly doses of 15 mg/kg maintained concentrations of > 40 microg/ml for the majority of patients.

Primary malignant melanoma of the lower respiratory tract. Report of a case and literature review.

The authors report a case of primary bronchial malignant melanoma, occurring in a 34-year-old woman presenting with persistent cough. At bronchoscopic examination, a polypoid mass was found to occlude the left mainstem bronchus. Biopsies showed a malignant epithelioid tumor resembling an atypical carcinoid. Histochemistry, electron microscopic study, and immunohistochemistry confirmed the diagnosis of melanoma. Physical examination and additional clinical history to exclude other possible primary sites were negative. The patient underwent thoracotomy with left pneumonectomy. Nineteen months after resection she was found to have a histologically similar tumor involving her left adrenal gland. Review of the literature shows that melanoma of the lower respiratory tract has been reported only in adults and has a tendency to present as a central polypoid growth that may be responsive to surgical resection.

CD44 expression in sinonasal inverted papillomas and associated squamous cell carcinoma.

Increased expression of the cell adhesion molecule, CD44 standard form (CD44s), has been associated with papillary epithelial tumors, and decreased expression has been linked to tumor invasion and metastasis. Sinonasal inverted papillomas (SIPs) are the most common papillary tumors of the sinonasal tract. This study tests whether the development of squamous cell carcinoma (SCC) in situ and invasive SCC in SIP is associated with altered expression of CD44s. Seventy-six specimens of SIP from 68 patients, 2 specimens of SIP with focal SCC in situ, and 10 specimens of invasive SCC arising in SIP were studied. Automated immunohistochemistry was performed for CD44s expression on paraffin-embedded tissue sections using mouse antihuman CD44 antibody. All 76 SIPs (100%) expressed CD44 (strong membranous staining, 83%; moderate staining, 12%; weak staining, 5%). Two (100%) of 2 SIPs with SCC in situ maintained strong expression in benign and severely dysplastic foci. Six (60%) of 10 SIPs with SCC showed complete loss of CD44s expression, while 4 (40%) of 10 cases of SIP with SCC showed weak expression. Two SIPs with SCC (20%) featured weak diffuse staining of the SCC component, and 2 SIPs with SCC (20%) featured weak focal staining of the SCC component. The non-SCC SIP components of the 10 SIPs with SCC uniformly featured intact membranous CD44 staining. As in other papillary epithelial neoplasms, the typical benign SIP features diffuse membranous CD44s expression. In cases of SIP developing an invasive SCC, CD44s expression in the SCC component is frequently lost.

Hemodynamic effects of anti-G suit inflation in a 1-G environment.

This study evaluated effects of various anti-G inflation pressures on cardiac volumes and the relationship of these volume changes to mean arterial pressure changes. Ventricular volumes were calculated using two-dimensional echocardiography. An anti-G suit was inflated to 2, 4, and 6 psi in the standing and supine positions for 10 male subjects. In the supine position, mean arterial pressure increased from base line for all three inflation pressures (P = 0.05). The end-diastolic volume increased after 2-psi inflation (P = 0.03). Cardiac output or stroke volume did not change. After standing, mean arterial pressure (P = 0.002), end-diastolic volume (P = 0.002), and stroke volume (P = 0.05) fell after suit deflation. Peripheral vascular resistance fell in the 2- and 4-psi inflation profiles. In the standing protocol, mean arterial pressure, end-diastolic volume, stroke volume, and cardiac output rose with all three inflation pressures (P less than 0.05). After reclining, heart rate increased (P = 0.02) and mean arterial pressure fell (P less than 0.05) in the 4- and 6-psi inflation profiles after suit deflation. Increases in mean arterial pressure are caused by increases in cardiac preload and cardiac output after inflation of the anti-G suit while subjects were standing. Increased cardiac preload was not consistently seen after inflation while subjects were supine. Changes in end-diastolic volume and mean arterial pressure were dependent on the pressure used to inflate the anti-G suit.

Long-duration +Gz acceleration on cardiac volumes determined by two-dimensional echocardiography.

To enhance protection of humans exposed to long-duration low-gravity environments such as the Space Shuttle and National Aerospace Plane during re-entry or in the short-duration high(-)+Gz environment of fighter aircraft, the effects of +Gz acceleration on cardiovascular hemodynamics must be understood. This study reports the use of two-dimensional echocardiography in normal men during +Gz acceleration. The heart's position in relation to the chest did not change during acceleration up to +7 Gz. The success in maintaining high-quality images during exposures to G-forces of this magnitude may be attributed to the relatively low rate of G onset. End-diastolic volumes (EDV) and stroke volumes (SV) decreased during a +Gz acceleration ramp that increased until the subject experienced peripheral light loss (PLL) (P < .05). An inflated G-suit partially counteracted this effect. By 30 seconds of a +3 Gz acceleration plateau, the protective effects of the inflated G-suit to maintain EDV is lost and the EDV of the inflated G-suit was lower than the EDV of the uninflated G-suit (P < .05).