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Biomedical subjects

L Pratt

Publications and source records attributed to L Pratt.

At least 19 recordsLinked to original sources

Intravitreal triamcinolone in subfoveal recurrence of choroidal neovascularisation after laser treatment in macular degeneration.

BACKGROUND: Laser treatment of extrafoveal well delineated choroidal neovascularisation in exudative age related macular degeneration has a high rate of failure with subsequent severe vision loss from subfoveal involvement. Laser treatment may limit scotoma size, but is unpalatable because of early persistent vision loss. Intravitreal triamacinolone injection may be an acceptable alternative therapy in such disparate cases. METHODS: 14 consecutive patients with recurrent neovascularisation were treated with a single 4.0 mg injection of triamacinolone and followed for up to 1 year. Visual results were compared with published data from the Macular Photocoagulation Study of recurrent neovascularisation. RESULTS: Mean visual acuity remained stable at about 20/200 throughout the study period in the treated patients. This is comparable to the outcomes in the Macular Photocoagulation Study for laser retreated patients, and better than the observation group. CONCLUSIONS: Intravitreal triamcinolone may be an acceptable treatment of subfoveal recurrent neovascularisation while avoiding early persistent vision loss from laser retreatment.

Anti-Inflammatory Agents↗

Anti-angiogenic therapy of proliferative diabetic retinopathy.

Proliferative diabetic retinopathy (PDR) remains one of the major causes of acquired blindness in developed nations. This is true despite the development of laser treatment, which can prevent blindness in the majority of those who develop this complication. The hallmark of PDR is neovascularisation (NV), abnormal angiogenesis that may ultimately cause severe vitreous cavity bleeding and/or retinal detachment. Pharmacologic therapy aimed at preventing NV, as an adjunct to laser treatment, or as an alternative to laser treatment, would be a welcome addition to the armamentarium. PDR could be prevented by improved metabolic control or by pharmacologically blunting the biochemical consequences of hyperglycaemia (e.g., with aldose reductase inhibitors, inhibitors of non-enzymatic glycation or by protein kinase C (PKC) inhibition). The angiogenesis in PDR could be treated via growth factor (e.g., vascular endothelial growth factor (VEGF), insulin like growth factor-1) blockade, integrin (e.g., alpha-v beta-3) blockade or extracellular matrix alteration (e.g., with steroid compounds), or interference with intracellular signal transduction pathways (e.g., PKC and mitogen activated protein kinase pathway proteins). Numerous potentially useful anti-angiogenic compounds are in development, but two drugs are presently in clinical trials for the treatment of the preproliferative stage of PDR.

Aldehyde Reductase↗

Acne keloidalis is a form of primary scarring alopecia.

OBJECTIVE: To better define the pathogenesis of acne keloidalis (AK). DESIGN: Prospective, blinded study of histologic material collected from 10 patients with clinically typical AK. SETTING: Outpatient dermatology clinic of a military tertiary care medical center. PATIENTS: Ten male volunteers 18 years or older with early AK lesions (1- to 4-mm firm papules on the lower occipital/nuchal region). DATA SOURCE: Biopsy specimens from small, early lesions and from clinically uninvolved skin, studied histologically with transverse sectioning. INTERVENTION: Three separate 4-mm punch biopsy specimens of the scalp (lesional, perilesional, and "normal" scalp) were obtained from each volunteer. The specimens were processed using transverse sectioning. MAIN OUTCOME MEASURES: The primary variables for data analysis were the presence or absence of the following histologic features: premature loss of the inner root sheath; eccentric placement of shaft, with thinning of the outer root sheath; lamellar fibroplasia surrounding the follicle; loss of sebaceous glands; evidence of follicular destruction or scarring; inflammation; and intrafollicular or perifollicular microorganisms. The number and type of hairs were also recorded. RESULTS: The most common findings in the 19 histologically abnormal specimens were perifollicular, chronic (lymphocytic and plasmacytic) inflammation, most intense at the level of the isthmus and lower infundibulum; lamellar fibroplasia, most marked at the level of the isthmus; complete disappearance of sebaceous glands, associated with inflamed or destroyed follicles; thinning of the follicular epithelium, most marked at the level of the isthmus; and total epithelial destruction (superficial and deep), with residual "naked" hair fragments. Even some "normal" specimens contained true follicular scars, demonstrating that normal-appearing scalp skin had previously been affected by the disease. CONCLUSIONS: Acne keloidalis is a primary form of scarring alopecia, and many of the histologic findings closely resemble those found in certain other forms of cicatricial alopecia. Extensive subclinical disease may be present in patients with AK and can account for some of the permanent hair loss. Overgrowth of microorganisms does not appear to play an important role in the pathogenesis of the disease. There is no etiologic relationship between AK and pseudofolliculitis barbae. Therapies found to be useful in other forms of inflammatory scarring alopecia are useful in the treatment of early AK.

Acne Keloid↗

Depositional facies and aqueous-solid geochemistry of travertine-depositing hot springs (Angel Terrace, Mammoth Hot Springs, Yellowstone National Park, U.S.A.).

Petrographic and geochemical analyses of travertine-depositing hot springs at Angel Terrace, Mammoth Hot Springs, Yellowstone National Park, have been used to define five depositional facies along the spring drainage system. Spring waters are expelled in the vent facies at 71 to 73 degrees C and precipitate mounded travertine composed of aragonite needle botryoids. The apron and channel facies (43-72 degrees C) is floored by hollow tubes composed of aragonite needle botryoids that encrust sulfide-oxidizing Aquificales bacteria. The travertine of the pond facies (30-62 degrees C) varies in composition from aragonite needle shrubs formed at higher temperatures to ridged networks of calcite and aragonite at lower temperatures. Calcite "ice sheets", calcified bubbles, and aggregates of aragonite needles ("fuzzy dumbbells") precipitate at the air-water interface and settle to pond floors. The proximal-slope facies (28-54 degrees C), which forms the margins of terracette pools, is composed of arcuate aragonite needle shrubs that create small microterracettes on the steep slope face. Finally, the distal-slope facies (28-30 degrees C) is composed of calcite spherules and calcite "feather" crystals. Despite the presence of abundant microbial mat communities and their observed role in providing substrates for mineralization, the compositions of spring-water and travertine predominantly reflect abiotic physical and chemical processes. Vigorous CO2 degassing causes a +2 unit increase in spring water pH, as well as Rayleigh-type covariations between the concentration of dissolved inorganic carbon and corresponding delta 13C. Travertine delta 13C and delta 18O are nearly equivalent to aragonite and calcite equilibrium values calculated from spring water in the higher-temperature (approximately 50-73 degrees C) depositional facies. Conversely, travertine precipitating in the lower-temperature (< approximately 50 degrees C) depositional facies exhibits delta 13C and delta 18O values that are as much as 4% less than predicted equilibrium values. This isotopic shift may record microbial respiration as well as downstream transport of travertine crystals. Despite the production of H2S and the abundance of sulfide oxidizing microbes, preliminary delta 34S data do not uniquely define the microbial metabolic pathways present in the spring system. This suggests that the high extent of CO2 degassing and large open-system solute reservoir in these thermal systems overwhelm biological controls on travertine crystal chemistry.

Calcium Carbonate↗

Repeated use of betamethasone in rabbits: effects of treatment variation on adrenal suppression, pulmonary maturation, and pregnancy outcome.

OBJECTIVE: The aim of the study was to determine whether reduced birth weight, adrenal suppression, and lung maturation occur in parallel and are cumulative with increasing courses of betamethasone. STUDY DESIGN: Time-bred rabbits were assigned to a control group or to receive saline solution or 1, 2, or 3 courses of betamethasone (early treatment, beginning day 19). Two additional groups (n = 5 per group) were given 1 or 2 late courses (late treatment). Birth weight, serum cortisol, adrenal 17alpha-hydroxylase (P450c17) messenger ribonucleic acid and fetal lung surfactant proteins A and B were quantified on day 27. RESULTS: Fetal weight was inversely proportional to the number of courses, with late treatment having a greater effect. Maternal cortisol and P450c17 levels were progressively suppressed with each early course, but fetal cortisol and P450c17 levels were only suppressed after 3 courses. A single late treatment profoundly suppressed both maternal and fetal cortisol and P450c17 messenger ribonucleic acid levels. In contrast, fetal lung surfactant proteins A and B increased progressively with betamethasone courses, regardless of timing. CONCLUSIONS: Time from last injection to delivery determined adrenal suppression, whereas total betamethasone courses determined surfactant protein production. Lower birth weight was dependent on the number of courses and was greater with late treatment.

3-Hydroxysteroid Dehydrogenases↗

Multiple vs. single betamethasone therapy. Neonatal and maternal effects.

OBJECTIVE: To identify potential neonatal benefits and possible neonatal and maternal complications associated with repeated use of antenatal corticosteroids. STUDY DESIGN: A retrospective chart review was done on all gravidas < 34 weeks who were hospitalized and received antenatal betamethasone at our institution between January 1, 1992 and April 30, 1996. Regression analysis was performed to investigate the relationship between single vs. multiple course of betamethasone and multiple variables. RESULTS: After controlling for significant covariates, multiple courses of betamethasone were associated with a decrease in oxygen use (P < .01). A nonsignificant decline in respiratory distress syndrome and assisted ventilation was noted. No effect on birth weight or maternal or neonatal infection was seen. CONCLUSION: Repeated use of betamethasone is associated with a significant decrease in oxygen use in the preterm neonate. No significant maternal or neonatal complications were found. A prospective, randomized trial is necessary.

Adult↗

Reversible fetal hydrops associated with indomethacin use.

BACKGROUND: Ductus arteriosus constriction is a known complication of exposure to indomethacin in utero. Nonimmune hydrops associated with indomethacin use has been reported in only six cases, all twins over 32 weeks' gestation. CASE: We present a case of fetal hydrops associated with tricuspid regurgitation and ductal constriction developing within 30 hours of instituting indomethacin tocolysis in a 28-week singleton gestation. Discontinuation of indomethacin resulted in partial resolution of these findings 72 hours later. A normal infant was delivered subsequently. CONCLUSION: Ultrasonographic screening for signs of constriction of the ductus arteriosus should be done within 48 hours of instituting indomethacin therapy at any gestational age.

Adult↗

Spontaneous regression of granulomatous mycosis fungoides in an HIV positive patient.

The development of mycosis fungoides in HIV-positive patients is uncommon. We describe the granulomatous type of mycosis fungoides in an HIV-positive patient whose cutaneous lesions regressed without treatment. In addition to HIV seropositivity and mycosis fungoides, he had a long history of pulmonary sarcoidosis. Immunophenotyping of the cutaneous lymphoid infiltrates revealed a predominance of CD4+ T cells, and monoclonality was demonstrated by T-cell gene rearrangement studies. The regression of mycosis fungoides in this patient was associated with a falling peripheral blood CD4 T-cell count.

Adult↗

Ultrasound detection of Apert syndrome: a case report and literature review.

Apert Syndrome is characterized by craniosynostosis, bilateral syndactyly, and midfacial hypoplasia. Although it was first described by Wheaton in 1894, it was first diagnosed prenatally only a decade ago-with only five cases reported in the literature. A sixth case is reported here. Prenatal diagnosis of Apert syndrome is reviewed.

Abortion, Therapeutic↗

Virus-like particles and E1-E4 protein expressed from the human papillomavirus type 11 bicistronic E1-E4-L1 transcript.

Detection of E1-E4 protein in human papillomavirus (HPV 11)-infected tissue is tightly linked to detection of L1 major capsid protein. The only L1-containing transcript identified in HPV 11-infected tissue is the bicistronic E1-E4-L1 mRNA, potentially encoding both the E1-E4 and the L1 proteins. It has not been established that these proteins can be expressed from the E1-E4-L1 transcript. The HPV 11 E1-E4-L1 sequence was cloned by reverse transcriptase polymerase chain reaction into the p1393 vector to produce recombinant baculoviruses. Immunoblots of recombinant baculovirus-infected Sf9 cell lysates demonstrated both the E1-E4 and the L1 proteins. An ELISA was performed on infected Sf9 cells using a monoclonal antibody specific for nondenatured L1, demonstrating that 10 ng of native L1 protein was present per microgram of total nuclear protein. Electron microscopic analysis revealed 50- to 60-nm icosahedral virus-like particles. In vitro transcription/translation was performed using pSPORT constructs containing the E1-E4-L1 sequence or, as controls, monocistronic pSPORT-E1-E4 or L1 constructs. The pSPORT-E1-E4-L1 construct produced the E1-E4 and L1 proteins at a ratio of 17:1. For E1-E4 protein, expression was greater from the pSPORT-E1-E4-L1 construct than from the monocistronic pSPORT-E1-E4 construct. In contrast, more L1 protein was expressed from pSPORT-L1 than from pSPORT-E1-E4-L1. A mutant E1-E4-L1 construct containing no E1-E4 start codon expressed L1 protein in amounts nearly equal to that expressed from the pSPORT-L1 construct. Addition of an antisense oligonucleotide directed at the E1-E4 start codon region to in vitro reactions using pSPORT-E1-E4-L1 was associated with inhibition of E1-E4 protein synthesis and increased translation of L1 protein.

Animals↗

Virus-like Particles and E1AE4 Protein Expressed from the Human Papillomavirus Type 11 Bicistronic E1AE4AL1 Transcript

Detection of E1AE4 protein in human papillomavirus (HPV 11)-infected tissue is tightly linked to detection of L1 major capsid protein. The only L1-containing transcript identified in HPV 11-infected tissue is the bicistronic E1AE4AL1 mRNA, potentially encoding both the E1AE4 and the L1 proteins. It has not been established that these proteins can be expressed from the E1AE4AL1 transcript. The HPV 11 E1AE4AL1 sequence was cloned by reverse transcriptase polymerase chain reaction into the p1393 vector to produce recombinant baculoviruses. Immunoblots of recombinant baculovirus-infected Sf9 cell lysates demonstrated both the E1AE4 and the L1 proteins. An ELISA was performed on infected Sf9 cells using a monoclonal antibody specific for nondenatured L1, demonstrating that 10 ng of native L1 protein was present per microgram of total nuclear protein. Electron microscopic analysis revealed 50- to 60-nm icosahedral virus-like particles. In vitro transcription/translation was performed using pSPORT constructs containing the E1AE4AL1 sequence or, as controls, monocistronic pSPORT-E1AE4 or L1 constructs. The pSPORT-E1AE4AL1 construct produced the E1AE4 and L1 proteins at a ratio of 17:1. For E1AE4 protein, expression was greater from the pSPORT-E1AE4AL1 construct than from the monocistronic pSPORT-E1AE4 construct. In contrast, more L1 protein was expressed from pSPORT-L1 than from pSPORT-E1AE4AL1. A mutant E1AE4AL1 construct containing no E1AE4 start codon expressed L1 protein in amounts nearly equal to that expressed from the pSPORT-L1 construct. Addition of an antisense oligonucleotide directed at the E1AE4 start codon region to in vitro reactions using pSPORT-E1AE4AL1 was associated with inhibition of E1AE4 protein synthesis and increased translation of L1 protein.

Journal Article↗

Temporal and histologic relationships of proliferating cell nuclear antigen and human papillomavirus type 11 in the mouse xenograft system.

Proliferating cell nuclear antigen (PCNA) is an accessory protein of DNA polymerase delta. This protein is associated with cell cycle progression and can be detected in the replicating cells of normal tissues. Condylomata acuminata are benign epithelial tumors caused by infection with human papillomaviruses and are characterized by abnormal cell proliferation. The athymic mouse xenograft model of HPV 11 infection was used to test the hypothesis that PCNA is induced early in the course of HPV 11 infection and to study the temporal and histologic relationships between detection of PCNA and HPV DNA. Human foreskin tissue was infected with HPV 11 and implanted under the renal capsules of 10 athymic mice. Pairs of mice were sacrificed every week beginning four weeks after implantation. HPV DNA was detected in sections of foreskin implants by in situ hybridization. PCNA was as or more abundant in implants removed at earlier time points than at later time points, whereas HPV DNA became increasingly more abundant with time. PCNA was detected only in basal cells in areas of histologically normal epithelium that were also negative for HPV DNA. In contrast, PCNA was present throughout the epithelium in regions that were HPV DNA-positive. HPV DNA was detected only in differentiated epithelial cells in implants removed at all five time points, but in HPV DNA-positive regions, PCNA was detected with equal intensity in differentiated and undifferentiated cells. The foci of PCNA-positive cells were well demarcated and were larger than, but included, the foci of HPV DNA-positive cells. PCNA may be induced maximally in differentiated epithelium by HPV 11 prior to significant HPV DNA replication.

Animals↗

Depression and risk for onset of type II diabetes. A prospective population-based study.

OBJECTIVE: To determine whether depression is associated with an increased risk for onset of diabetes. RESEARCH DESIGN AND METHODS: In 1981, a total of 3,481 household-residing adults participated in the Epidemiologic Catchment Area (ECA) Program survey at the East Baltimore site. A follow-up of that cohort after 13 years completed 1,897 interviews, amounting to > 72% of survivors. In 1981, depression was assessed with the National Institutes of Mental Health (NIMH) Diagnostic Interview Schedule and diabetes, by self-report. This prospective analysis focused on subjects at risk for onset of diabetes by removing from the analysis individuals with diabetes in 1981. RESULTS: There were 89 new cases of diabetes among 1,715 individuals at risk, yielding a 13-year cumulative incidence of diabetes of 5.2%. In logistic models, major depressive disorder, but not milder forms of depression or other forms of psychiatric disorder, predicted the onset of diabetes (estimated relative risk, 2.23; 95% CI 0.90-5.55). Controlling for age, race, sex, socioeconomic status, education, use of health services, other psychiatric disorders, and body weight did not weaken the relationship. CONCLUSIONS: Major depressive disorder signals increased risk for onset of type II diabetes. Limitations of the findings arise from the difficulty in determining temporal order with two chronic conditions, even when the temporal order of measurement is clear. In addition, even though control variables were introduced for the use of health services, it is possible that the treatment for depression led to an earlier diagnosis of diabetes in this sample.

Adult↗