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Biomedical subjects

G Dreyer

Publications and source records attributed to G Dreyer.

At least 19 recordsLinked to original sources

Management of recurrent cervical cancer.

Treatment for cervical cancer is very successful, especially in early stages. However, most patients presenting in late stages of disease will experience recurrence. The prognosis of recurrent disease is very poor and treatment options are limited. The diagnosis of recurrence may be apparent or difficult, but determining the extent of disease is always complex. Routine follow-up of asymptomatic patients has other objectives and is not a reliable way to detect recurrences. Symptomatic patients require extensive investigation to detect the extent of the disease. For patients with central pelvic recurrences, exenteration offers the prospect of survival in more than one-third of cases. Newer developments include laterally extended endopelvic resection that may become an option for patients with more extensive pelvic recurrence. For patients with recurrences of cervical cancer, the roles of second-time radiotherapy or postradiation chemotherapy are very limited. Palliative treatment is important for all patients with untreatable disease. Pain relief forms a central part of palliative care. Caregivers also experience emotional feelings and probably function best in a system offering strong colleageal support.

Female↗

Operative management of cervical cancer.

Radical abdominal hysterectomy with pelvic lymph node dissection remains the treatment of choice for most patients with early-stage cervical cancer. The radicality and extent of lymph node dissection and parametrial resection should be tailored to tumour- and patient-related risk factors. Adjuvant therapy after radical surgery improves local control in high-risk patients and some intermediate-risk patients. The absolute indications for adjuvant therapy include multiple or macroscopically involved nodes, parametrial invasion and positive surgical margins. Adjuvant therapy may be given as chemoradiation or as radiotherapy alone, depending on risk assessment and expected morbidity. Primary chemoradiation is an equally effective alternative, but adjuvant surgery or finishing hysterectomy after pelvic radiation is not beneficial. Promising new developments include neo-adjuvant chemotherapy followed by surgery for bulky early-stage disease, tailoring radicality to reduce therapeutic morbidity and integrating minimal access surgical techniques into current treatment protocols.

Blood Transfusion↗

Bancroftian filariasis in children and adolescents: clinical-pathological observations in 22 cases from an endemic area.

In areas where bancroftian filariasis is endemic, the clinical manifestations of the disease, which are often very varied, appear most frequently during early adulthood or later. In consequence, very little attention, if any, has been given to the signs and symptoms of the disease in childhood. In an attempt to fill this gap, clinical and pathological observations were made, in Brazil, on 22 children (aged 2-15 years) who were infected with Wuchereria bancrofti. There was a predominance of lymph-node involvement. In all but three (14%) of the children (who had adult parasites in their intrascrotal lymphatic vessels), the adult worms were located in the afferent or efferent vessels of draining lymph nodes, predominantly in the inguinal region. None of the patients presented with distal lymphoedema, and the adenopathy was characterized by painless, localized, lymph-node enlargement, without signs of inflammation in the overlying skin. Histologically, the alterations in the lymphatic vessels and surrounding structures were similar to those described in adult patients, and depended essentially on adult-parasite viability. The localization of the adult worms in the paediatric cases was peculiar and distinct from that observed in adult patients, in whom the adult parasites are usually found in extra-nodal lymphatic vessels. In areas endemic for bancroftian filariasis, therefore, filarial infection should be considered as a possible cause of adenopathy. For the differential diagnosis of adenopathy in young patients from endemic areas, the authors recommend the use of ultrasound and other non-invasive diagnostic tools, as alternatives to excisional biopsies, which are often unnecessary in bancroftian filariasis.

Adolescent↗

PTEN mutations in uterine sarcomas.

OBJECTIVE: Uterinesarcomas comprise three main types: carcinosarcomas, leiomyosarcomas, and endometrial stromal sarcomas. Carcinosarcomas are highly aggressive neoplasms with a biphasic histology of carcinomatous and sarcomatous elements. It is now generally accepted that carcinosarcomas are biphasic tumors that have to be regarded as endometrial carcinomas where metaplasia occurs. Mutations of the PTEN tumor suppressor gene, located on 10q23, play a significant role in the pathogenesis of the endometrioid type of endometrial carcinoma. Loss of heterozygosity of chromosome 10q has been reported in uterine leiomyosarcoma. Since little is known about the molecular pathobiology, our goal was to investigate the potential role of the PTEN gene in the carcinogenesis of uterine sarcomas. METHODS: We examined 21 carcinosarcomas, 21 leiomyosarcomas, and 5 endometrial stromal sarcomas using exon-by-exon polymerase chain reaction-single-strand conformation polymorphism analysis. RESULTS: Overall 8.5% (4/47) of uterine sarcomas were found to harbor somatic PTEN mutations. Of these, approximately 17% (3/18) were carcinosarcomas with endometrioid-type carcinoma components and approximately 5% (1/21) were leiomyosarcomas. No mutations were detected in carcinosarcomas with nonendometrioid carcinoma components (0/3) and in endometrial stromal sarcomas (0/5). CONCLUSIONS: These data suggest that intragenic PTEN mutations are involved in the genesis of uterine carcinosarcomas with endometrioid-type carcinoma components but rarely contribute to the pathobiology of uterine leiomyosarcomas.

Exons↗

The histopathology of bancroftian filariasis revisited: the role of the adult worm in the lymphatic-vessel disease.

Although morphology is generally limited to static images, the histopathological features of bancroftian lymphatic disease are presented here in a way that is as dynamic as possible and closely associated with the clinical, ultrasonographic and surgical characteristics. The protean spectrum of alterations seen in the host's lymphatic vessels is discussed, and the changes caused by the live and dead worms are highlighted, as independent events. Evidence of a remodelling process, in which the lymphatic endothelial cells appear to have a key role, is provided for the first time. Despite many new pieces of information, there remain many 'blank pages' in the natural history of bancroftian filariasis.

Animals↗

Lymphatic filariasis in children: adenopathy and its evolution in two young girls.

Lymphatic filariasis is a widespread infectious disease of children in endemic areas, but little is known about the early lymphatic damage in children and its evolution, either with or without treatment. Two girls (ages 6 and 12 years) from a Wuchereria bancrofti endemic region of Brazil presented with chronic inguinal adenopathy. Neither had microfilaremia. By ultrasound both were shown to have living adult worms in their enlarged inguinal nodes and had occult local lymphatic damage (lymphangiectasis). One girl spontaneously developed acute adenitis in the affected node prior to any intervention; this adenitis resolved within 10 days and was associated with the progressive disappearance over 45-90 days of all local abnormalities detectable by ultrasound. In the other child, after treatment with a single dose of diethylcarbamazine (DEC), the same clinical picture of transient adenitis and resolving abnormalities (detectable by ultrasound) occurred. These findings demonstrated filariasis as the cause of adenopathy in children, and also both spontaneous and treatment-induced worm-death, with subsequent reversal of lymphatic abnormalities.

Animals↗

Actinonin, a naturally occurring antibacterial agent, is a potent deformylase inhibitor.

Peptide deformylase (PDF) is essential in prokaryotes and absent in mammalian cells, thus making it an attractive target for the discovery of novel antibiotics. We have identified actinonin, a naturally occurring antibacterial agent, as a potent PDF inhibitor. The dissociation constant for this compound was 0.3 x 10(-)(9) M against Ni-PDF from Escherichia coli; the PDF from Staphylococcus aureus gave a similar value. Microbiological evaluation revealed that actinonin is a bacteriostatic agent with activity against Gram-positive and fastidious Gram-negative microorganisms. The PDF gene, def, was placed under control of P(BAD) in E. coli tolC, permitting regulation of PDF expression levels in the cell by varying the external arabinose concentration. The susceptibility of this strain to actinonin increases with decreased levels of PDF expression, indicating that actinonin inhibits bacterial growth by targeting this enzyme. Actinonin provides an excellent starting point from which to derive a more potent PDF inhibitor that has a broader spectrum of antibacterial activity.

Amidohydrolases↗

Pathogenesis of lymphatic disease in bancroftian filariasis: a clinical perspective.

The pathogenesis of lymphatic filariasis has been a matter of debate for many decades. Here, Gerusa Dreyer and colleagues propose a dynamic model of bancroftian filariasis, integrating clinical, parasitological, surgical, therapeutic, ultrasonographic and histopathological data. This model has profound implications for filariasis control programs and the management of the individual patient.

Albendazole↗

Longitudinal evaluation of growth, puberty, and bone maturation in children with Williams syndrome.

OBJECTIVES: To establish syndrome-specific growth curves and growth rate (GR) curves for Williams syndrome (WS) and define the pattern of bone maturation and pubertal development. METHODS: In a prospective longitudinal study between 1990 and 1997, the growth data of 244 children with WS were collected: 295 values for GR were calculated for 74 girls and 331 values for 89 boys. RESULTS: Mean GR of children with WS was below normal by 1 to 2 cm/y in the first few years of life. One group of girls (n = 20) experienced an early pubertal growth spurt at age 9 years (maximal GR, 7.8 +/- 2.1 cm/y; menarcheal age, 10.4 +/- 1.4 years). A second group (n = 5) showed the growth spurt at age 11 years (7.5 +/- 1.1 cm/y; menarcheal age, 12.6 +/- 1.3 years). In boys, peak height velocity (8.7 +/- 2.3 cm/y) occurred at age 11 to 12 years. Bone age was delayed in both sexes during childhood and accelerated markedly during puberty. Final height was 152.4 +/- 5.7 cm in girls (n = 38) and 165.2 +/- 10. 9 cm in boys (n = 43). CONCLUSIONS: The syndrome-specific GR curves for WS showed a premature and abbreviated pubertal growth spurt in both sexes. This growth spurt was directly related to bone age acceleration during puberty. The data from this longitudinal study provide an overview of both the dynamics of growth and its course in children with WS.

Body Height↗

Screening of army soldiers for Wuchereria bancrofti infection in the metropolitan Recife region, Brazil: implications for epidemiological surveillance.

Between 1989 and 1995, blood surveys were performed for Wuchereria bancrofti infection in several barracks of the Brazilian army in the metropolitan Recife region. For initial screening, 60 microliters of capillary blood were examined for microfilaria. All men who tested positive had microfilaria quantified by filtration of venous blood through a polycarbonate membrane. Of 23,773 men screened, 585 (2.5%) had microfilaria (mf). Microfilarial density ranged from < 1-8706 mf/ml of blood. Thirteen individuals had ultra-low microfilarial densities (1 mf/11 ml of blood). Characterization of 174 autochthonous cases made it possible to map 8 new districts in 4 cities within metropolitan Recife region where transmission of W. bancrofti was previously unknown. Routine screening of soldiers in the military may provide important surveillance data for national programmes to eliminate transmission of W. bancrofti.

Adolescent↗

Proposed panel of diagnostic criteria, including the use of ultrasound, to refine the concept of 'endemic normals' in lymphatic filariasis.

Although living adult Wuchereria bancrofti worms can be detected by ultrasound examination of the scrotal area in approximately 80% of men infected with this filarial parasite, the location of the adult worms in the remaining 20% remains unclear. To determine this, 32 individuals who had W. bancrofti microfilaraemia but no adult worms detectable on ultrasound were treated with diethylcarbarmazine (DEC), either with a single 6 mg/kg dose (n = 13) or with a 12-day course of 6 mg/kg per day (n = 19). They were then monitored with serial physical and ultrasound examinations. Thirteen (41%) subjects developed small, single scrotal nodules 12 h to 7 days after treatment; this rate was unaffected by the dose of DEC. No nodules were detected outside the scrotal area. All 5 men with lymphangiectasia suspected on ultrasound before treatment developed scrotal nodules, compared to 8 (29.6%) of 27 men without ultrasonographic evidence (P = 0.006). Thus, using both ultrasound and 'provocative' treatment with DEC, adult W. bancrofti can be detected in the scrotal area of an estimated 88% of infected men. Because no single diagnostic test for W. bancrofti infection is completely sensitive, a panel of tests, including ultrasound, is proposed to identify with greater accuracy 'endemic normals' for immunological and epidemiological studies.

Adult↗

Extralymphatic disease due to bancroftian filariasis.

Infection with Wuchereria bancrofti, Brugia malayi, or B. timori not only affects the structure and function of lymphatic vessels but is also associated with extralymphatic pathology and disease. Because it is now possible to detect living adult worms by ultrasonography, much emphasis is placed on lymphatic pathology. However, the finding of renal damage in asymptomatic microfilaremic carriers has led to increased recognition of the importance of extralymphatic clinical manifestation in bancroftian filariasis. The authors present a number of clinical syndromes that may be manifestations of extralymphatic filarial disease and discuss possible mechanisms that cause these conditions. The main purpose of this paper is to raise the awareness of students and physicians of the prevalence and the importance of extralymphatic disease in bancroftian filariasis so that it is diagnosed and treated properly and also to alert for the need of additional research in this area.

Animals↗

Immunocytochemical localization and distribution of human albumin in Wuchereria bancrofti adult worms.

To determine whether albumin is present on adult worms of Wuchereria bancrofti, thin sections of resin-embedded parasites were incubated with a specific antiserum to human albumin. With the exception of the epicuticle, all layers of the cuticle and the hypodermis were intensely labeled. Concentration of gold particles was observed within infoldings of the hypodermal membrane. Moderate labeling of the thin basement membrane that lines the pseudocelomic cavity and the gonoduct was also observed. Within the uterus, ovular membranes labeled intensely; groups of organized particles were seen below ovular membranes and also within invaginations of microfilarial embryos. In contrast, few gold particles were seen on the surface of mature intrauterine microfilariae. No labeling was observed in control sections incubated with antiserum preadsorbed with purified human albumin. The findings suggest that human albumin may be essential for the nutrition and development of W bancrofti microfilariae.

Albumins↗

Ultrasonographic detection of living adult Wuchereria bancrofti using a 3.5-MHz transducer.

Adult Wuchereria bancrofti can be readily detected by ultrasound in the lymphatic vessels of the spermatic cord with a 7.5-MHz transducer, but most ultrasound machines in developing countries are equipped with 3.5-MHz transducers. To assess the potential for ultrasound as a tool for diagnosis and epidemiologic assessment in lymphatic filariasis, we compared the performance of 3.5-MHz and 7.5-MHz transducers in 61 men in Recife, Brazil. All men had three ultrasound examinations using a 3.5 MHz transducer and an examination with a 7.5-MHz probe. Using the 7.5-MHz transducer, adult W. bancrofti were detected in 41 men; 81 adult worm nests were detected. Sixty-four (79%) nests were detected with the 3.5-MHz probe, each on all three examinations. The 3.5-MHz probe correctly identified 35 (85.4%) of 41 men as infected; sensitivity increased with lymphatic vessel diameter. Ultrasonographic examination with a 3.5-MHz transducer is a sensitive method for detection of adult W. bancrofti in men and merits consideration as a tool for rapid epidemiologic assessment.

Adolescent↗

[Lymphatic filariasis: a potentially eradicable disease]

The recent demonstration that single-dose ivermectin, diethylcarbamazine, or a combination of these drugs can profoundly suppress Wuchereria bancrofti and Brugia malayi microfilaremia for periods of six months to two years has led to renewed hope that transmission can be interrupted and lymphatic filariasis eradicated. Based in part on the availability of these new chemotherapeutic tools, the International Task Force for Disease Eradication recently identified lymphatic filariasis as one of the few diseases that could potentially be eradicated. Thus, control programs based on mass treatment (whether supplemented or not by vector control) have begun to be implemented in some endemic areas. We provide a brief review of available anti-filarial drugs for use in humans, including their tolerance and efficacy.

Journal Article↗

Ultrasonographic assessment of the adulticidal efficacy of repeat high-dose ivermectin in bancroftian filariasis.

Since diethylcarbamazine, the drug recommended for treatment of lymphatic filariasis, seems only partially effective against the adult worm, intense interest persists in identifying a macrofilaricidal drug for this infection. To evaluate directly in vivo the macrofilaricidal activity of repeat high-dose ivermectin, 15 men who had living adult Wuchereria bancrofti detected in the scrotal area by ultrasound were treated with 400 micrograms/kg of ivermectin at 2-week intervals for 6 months (total dose, 4.8 mg/kg). Serial ultrasound examinations were performed before, during, and for 6 months after treatment. Profound suppression of microfilaraemia followed the first dose of ivermectin, but movements characteristic of the adult worm on ultrasound remained unchanged both in location and pattern. Even when given in total doses of 4.8 mg/kg, ivermectin appears to have no observable activity against adult W. bancrofti, although its ability to suppress microfilaraemia makes it potentially useful for the control of lymphatic filariasis.

Adult↗

Ultrasonographic evidence of abnormal lymphatic vessels in young men with adult Wuchereria bancrofti infection in the scrotal area.

PURPOSE: We determined the prevalence and magnitude of dilatation of the lymphatic vessels of the spermatic cord in men infected with Wuchereria bancrofti, which is known major cause of hydrocele in the tropics. MATERIALS AND METHODS: Scrotal ultrasound was performed with a 7.5 MHz, transducer in 78 men from Recife, Brazil (endemic for filariasis) and in 15 from a nonendemic area. RESULTS: Among men from Recife the lymphatic vessels were dilated (1.3 to 15.0 mm., mean 3.8) at the location of the adult worm. Vessel diameter was not associated with hydrocele. CONCLUSIONS: Lymphatic dilation was observed in all men with ultrasonographically detectable W. bancrofti infection, even those who were asymptomatic.

Adolescent↗