Prenatal ultrasonography and early surgery for congenital cystic disease of the lung.

With the recent advent of prenatal ultrasound as a routine screening procedure, diagnosis of congenital cystic lung disease has been made in utero, raising the possibility of elective surgery for these lesions early in infancy before the patient develops respiratory distress or potentially life-threatening infection. From 1979 to 1989 six cases of congenital lung cyst were diagnosed in utero by prenatal ultrasound and followed during pregnancy. Two of the six were not confirmed after birth because the mothers preferred an abortion. The remaining four cases were studied periodically during gestation by ultrasonography. At birth, the first infant developed respiratory distress and underwent urgent left upper lobectomy and left lower segmentectomy at age 18 hours. The other three underwent elective lobectomy at age 10 days, 3 months, and 7 months, respectively. The fourth infant had a normal chest x-ray and ultrasound at birth, and the congenital cysts were confirmed by computed tomography scan. The pathological diagnosis in all four cases was cystic adenomatoid malformation. In two cases, intraoperative measurement of pulmonary function demonstrated significant improvement after resection of the affected lobe. We conclude that congenital lung cysts can be accurately diagnosed by prenatal ultrasound "screening" as early as 18 to 24 weeks' gestation. Advantages of early diagnosis include the option of moving the mother and unborn child to a high-risk obstetrical center for urgent operation on the newborn infant if necessary. Otherwise, once the diagnosis is confirmed, surgical correction can be performed electively and safely before respiratory distress or pulmonary infection complicates the infant's growth and development.     

Fatal adenovirus pneumonia: Clinical and pathological features.

A review of autopsies of 107 young children with pneumonia showed that 15 children (14%) had adenovirus infections, the diagnosis being based on characteristic histopathological and ultrastructural features in the lungs. Eleven (73%) of the cases of adenovirus infection followed on measles infection, and it is suggested that some became infected with adenovirus after admission to hospital. A review of clinical aspects revealed no unique features. Histopathological examination of tissues showed a common picture of necrotising bronchopneumonia, with minor degrees of rental tubular damage, infiltrates of large mononuclear cells in spleen and nodes, and an absence of lymphoid germinal centres. On light microscopy, "rosette" and "smudge" cells were seen in these cases, and two patterns of virus particle distribution in infected cells were seen ultrastructurally. It is postulated that "smudge" cells contain numerous crystalline viral arrays.     

Executive function and verbal working memory in adolescents with closed head injury (CHI)

The relationship between executive function (EF) and working memory (WM) was studied in eight adolescents with closed head injury (CHI) and eight controls, matched for age, gender and socioeconomic status (SES). A cognitive-linguistic test (Scales of Cognitive Ability for Traumatic Brain Injury, SCATBI) was used to group CHI participants by severity. EF was tested with a measure of daily functioning (Pro-Ex) and WM was tested with a recognition memory task (RMT). When all subject test data were grouped, a positive linear correlation was found for the Pro-Ex and the RMT. A strongto-moderate positive correlation was found for components of the EF measure and the RMT. Severity of injury influenced test performance for both the EF and WM measures, with a significance between group effects found on the RMT task. Results indicate a relationship between executive function and working memory, severity of injury and test performance and the need to assess EF of CHI adolescents with a measure of daily functioning.     

Decreasing allergic contact dermatitis frequency through dermatotoxicologic and epidemiologic based intervention?

Allergic contact dermatitis (ACD) affects millions of people worldwide. In an attempt to decrease the incidence of contact dermatitis, several countries have implemented legislations to reduce the population's exposure to known sensitizers. To determine whether these legislations have been effective, we reviewed several studies examining trends in patch test reactivity before and after implementation of these legislations. Common sensitizers studied include nickel, gluceryl monothioglycolate fragrances, chromate, and thiuram. Overall, the evidence suggests a decreasing trend of ACD with appropriate formulation changes, however some of the data may be confounded by biases, and additionally, exposure to the sensitizer may still exist via non-compliance to regulations by small manufacturers. In the future population based studies should be conducted to more accurately assess trends in ACD.     

A phase I trial of the dual farnesyltransferase and geranylgeranyltransferase inhibitor L-778,123 and radiotherapy for locally advanced pancreatic cancer.

PURPOSE: Preclinical and clinical studies have demonstrated that inhibition of prenylation can radiosensitize cell lines with activation of Ras and produce clinical response in patients with cancer. The aim of this study was to determine the maximally tolerated dose of the dual farnesyltransferase and geranylgeranyltransferase I inhibitor L-778,123 in combination with radiotherapy for patients with locally advanced pancreatic cancer. EXPERIMENTAL DESIGN: L-778,123 was given by continuous intravenous infusion with concomitant radiotherapy to 59.4 Gy in standard fractions. Two L-778,123 dose levels were tested: 280 mg/m2/day over weeks 1, 2, 4, and 5 for dose level 1; and 560 mg/m2/day over weeks 1, 2, 4, 5, and 7 for dose level 2. RESULTS: There were no dose-limiting toxicities observed in the eight patients treated on dose level 1. Two of the four patients on dose level 2 experienced dose-limiting toxicities consisting of grade 3 diarrhea in one case and grade 3 gastrointestinal hemorrhage associated with grade 3 thrombocytopenia and neutropenia in the other case. Other common toxicities were mild neutropenia, dehydration, hyperglycemia, and nausea/vomiting. One patient on dose level 1 showed a partial response of 6 months in duration. Both reversible inhibition of HDJ2 farnesylation and radiosensitization of a study patient-derived cell line were demonstrated in the presence of L-778,123. K-RAS mutations were found in three of the four patients evaluated. CONCLUSIONS: The combination of L-778,123 and radiotherapy at dose level 1 showed acceptable toxicity in patients with locally advanced pancreatic cancer. Radiosensitization of a patient-derived pancreatic cancer cell line was observed.     

Classification of clear-cell sarcoma as a subtype of melanoma by genomic profiling.

PURPOSE: To develop a genome-based classification scheme for clear-cell sarcoma (CCS), also known as melanoma of soft parts (MSP), which would have implications for diagnosis and treatment. This tumor displays characteristic features of soft tissue sarcoma (STS), including deep soft tissue primary location and a characteristic translocation, t(12;22)(q13;q12), involving EWS and ATF1 genes. CCS/MSP also has typical melanoma features, including immunoreactivity for S100 and HMB45, pigmentation, MITF-M expression, and a propensity for regional lymph node metastases. MATERIALS AND METHODS: RNA samples from 21 cell lines and 60 pathologically confirmed cases of STS, melanoma, and CCS/MSP were examined using the U95A GeneChip (Affymetrix, Santa Clara, CA). Hierarchical cluster analysis, principal component analysis, and support vector machine (SVM) analysis exploited genomic correlations within the data to classify CCS/MSP. RESULTS: Unsupervised analyses demonstrated a clear distinction between STS and melanoma and, furthermore, showed that CCS/MSP cluster with the melanomas as a distinct group. A supervised SVM learning approach further validated this finding and provided a user-independent approach to diagnosis. Genes of interest that discriminate CCS/MSP included those encoding melanocyte differentiation antigens, MITF, SOX10, ERBB3, and FGFR1. CONCLUSION: Gene expression profiles support the classification of CCS/MSP as a distinct genomic subtype of melanoma. Analysis of these gene profiles using the SVM may be an important diagnostic tool. Genomic analysis identified potential targets for the development of therapeutic strategies in the treatment of this disease.     

Effectiveness and safety of loop electrosurgical excision procedure in a low-resource setting

Objective

To evaluate the effectiveness and safety of the loop electrosurgical excision procedure (LEEP) to treat cervical intraepithelial neoplasia (CIN) in a low-resource setting.

Methods

Women participating in a cervical screening study in India with histologically confirmed CIN unsuitable for cryotherapy were advised to undergo LEEP. One year after treatment the cervix was visually inspected with acetic acid, followed by colposcopy and biopsy taken from abnormal areas. Cure was defined as no clinical or histologic evidence of CIN. Factors influencing cure rates were evaluated by ^χ2 tests.

Results

Of the 311 women who underwent LEEP, 283 reported for 1-year follow-up and 248 (87.6%) were disease free. Cure rates were 93.0% for CIN 1, 85.5% for CIN 2, and 72.7% for CIN 3. Minor adverse effects were observed in 34 women and complications were seen in 5 women.

Conclusion

LEEP was associated with minimal complications and acceptable cure rates in a low-resource setting, although women with larger lesions had lower cure rates.     

Isolation and structure determination of two microcystins and sequence comparison of the McyABC adenylation domains in Planktothrix species

Microcystins (MCs) are toxic heptapeptides found in cyanobacteria and share the common structure cyclo(-d-Ala(1)-l-X(2)-d-isoMeAsp(3)-l-Z(4)-Adda(5)-d-isoGlu(6)-Mdha(7)). The letters X and Z in the general formula above represent a wide range of l-amino acids that occupy positions 2 and 4, respectively. In general the variation in structural variants is due to the exchange of amino acids in position 7, 2, and 4. In the present work we report two homotyrosine (Hty)-containing microcystin variants, [d-Asp(3),(E)-Dhb(7)]-MC-HtyY (1) and [d-Asp(3),(E)-Dhb(7)]-MC-HtyHty (2), which were isolated from strain No80 of Planktothrix rubescens. Their structures were elucidated using amino acid analysis as well as 1D and 2D NMR techniques. The adenylation domains of McyABC involved in amino acid activation in positions 7, 2, and 4 of the microcystin molecule, respectively, were compared with corresponding genes of Planktothrix strain CYA126/8 producing [d-Asp(3),Mdha(7)]-MC-RR and [d-Asp(3),Mdha(7)]-MC-LR. While the adenylation domain comparison of McyAB between the two Planktothrix strains revealed considerable DNA recombination, the adenylation domain of McyC showed only a single amino acid substitution, which was correlated with the replacement of Arg by Hty in position 4 of the microcystin molecule.