Amikacin alone and in combination with trimethoprim-sulfamethoxazole in the treatment of actinomycotic mycetoma

We report the excellent therapeutic response obtained with amikacin alone and in combination with trimethoprim-sulfamethoxazole in the treatment of 15 patients with actinomycotic mycetoma who had a poor response to the traditional pharmacologic agents and/or in whom important organs such as lungs, spinal cord, and bone were involved. We evaluated the results by clinical, radiologic, and laboratory tests. No important side effects were detected during or after the therapy.     

Regulation of major histocompatibility complex (MHC) products in fresh and cultured human fetal pancreata aged 9–16 gestational weeks by gamma-interferon

Immunological data on the human fetal pancreas (HFP) are mainly confined to its constitutive expression of the MHC antigens. However, cytokines, such as gamma-interferon (g-IFN), released by lymphocytes during immune reactions, can induce or upregulate the expression of MHC products in allografts and alter their immunological behaviour. We investigated the effects of g-IFN on fresh and cultured HFPs aged 9–16 gestational weeks (gw). Following g-IFN stimulation of fresh HFPs, there was class I hyperexpression by the ductal cells, and some of the ductal, endothelial and islet cells also became class II⁺. Conventional tissue culture (5% CO₂ in air at 37°C) reduced the number of interstitial class II⁺ cells within the HFP after 1 week but was associated with de novo class I expression by some of the ductal cells. Remarkably, the changes in major histocompatibility complex (MHC) antigen expression by the ductal cells occurred earlier and were markedly enhanced when the HFPs were cultured beforehand. The number of interstitial class II⁺ cells in fresh and cultured HFPs was not influenced by g-IFN. The significance of these observations with regard to clinical HFP transplantation is discussed.     

Volumetric interstitial hyperthermia: nursing implications for brain tumor treatment

Malignant glioma is a devastating disease which presents a clinical challenge to physicians and neuroscience nurses. It carries a dismal prognosis, with a median survival of only nine months following application of conventional therapies of surgical resection, radiotherapy and chemotherapy. Hyperthermia is the application of sufficient heat to raise the temperature in a volume of tumor to cytocidal levels. Patient tolerance and response to volumetric interstitial hyperthermia treatment in this clinical study of over 40 patients has been extremely encouraging. Hyperthermia, as part of multi-modality treatment of brain tumors, presents a change in the nursing management of this patient population. The neuroscience nurse plays a crucial role in linking clinical observations to decisions of patient management and treatment planning. Because hyperthermia is a new treatment modality, nurses, patients and families require additional education and extended support during therapy.     

Nonimmune hydrops caused by massive fetomaternal hemorrhage and treated by intravascular transfusion.

Fetal hydrops at 26 weeks' gestation was diagnosed following a massive fetomaternal hemorrhage. Fetal intravascular transfusion was performed, and the hydrops completely resolved within 72 hours. The fetus required one more transfusion at 27 weeks' gestation. A subsequent percutaneous umbilical blood sampling at 30 weeks' gestation demonstrated a normal fetal hematocrit. A vaginal delivery at term resulted in a normal newborn. Massive fetomaternal hemorrhage is a well-known cause of nonimmune hydrops and may occur spontaneously in an otherwise normal pregnancy. Confirmation by percutaneous umbilical blood sampling and treatment by intravascular transfusion is recommended when massive fetomaternal hemorrhage causes hydrops in preterm gestations.     

p53 mutation and protein accumulation during multistage human esophageal carcinogenesis.

Preinvasive lesions of squamous cell carcinoma are well defined morphologically and provide a model for multistage carcinogenesis. Since alterations in the p53 tumor suppressor gene occur frequently in invasive esophageal squamous cell carcinoma, we examined a set of preinvasive lesions to investigate the timing of p53 mutation. Surgically resected tissues from nine patients with esophageal squamous cell carcinoma contained precursor lesions which had not yet invaded normal tissues. Immunohistochemistry showed high levels of p53 protein in both preinvasive lesions and invasive carcinomas in six cases; sequence analysis of all invasive tumors identified p53 missense mutations in two cases. Preinvasive lesions from both tumors with mutations plus one wild-type tumor were microdissected and sequenced. In one patient there were different mutations in the invasive carcinoma (codon 282, CGGarg > TGGtrp) and a preinvasive lesion (codon 272, GTGval > T/GTGleu/val). In a second case, an invasive carcinoma had a mutation in codon 175 (CGCarg > CAChis), and adjacent preinvasive lesions contained a wild-type sequence. A carcinoma and preinvasive lesion from the third case contained high levels of protein and a wild-type DNA sequence. Therefore, p53 mutation may precede invasion in esophageal carcinogenesis, and multifocal esophageal neoplasms may arise from independent clones of transformed cells. The timing of p53 protein accumulation is favorable for an intermediate biomarker in multistage esophageal carcinogenesis.     

Detection and staging of dementia in Alzheimer's disease. Use of the neuropsychological measures developed for the Consortium to Establish a Registry for Alzheimer's Disease.

Our earlier studies using the Consortium to Establish a Registry of Alzheimer's Disease neuropsychological battery showed that delayed recall was a highly sensitive indicator of early Alzheimer's disease. None of the learning and memory measures in the battery were found to be useful in staging the severity of this form of dementia. This study explores the nonmemory functions (fluency, naming, and praxis) of the Consortium to Establish a Registry of Alzheimer's Disease battery and asks whether performance on any of these measures adds to the detection of early Alzheimer's disease or is sensitive to the later progression of the illness. We stratified patients with this disease according to severity (mild, moderate, severe), and compared them with age-, education-, and gender-matched control subjects (group N = 49 each). Multivariate procedures and cutting scores were used to determine the efficacy of the various measures in distinguishing between the cases and control subjects. Impairment of delayed recall was again found to be the best discriminator for detecting mild cases of Alzheimer's disease. Confrontation naming was the only nonmemory factor that assisted in this discrimination. For staging the illness, a combination of measures including fluency, praxis, and recognition memory best differentiated cases with mild dementia from those with either moderate or severe stages of disease. Measures of delayed recall quickly "bottomed out" in the patients with Alzheimer's disease and proved of little value in staging the disorder.(ABSTRACT TRUNCATED AT 250 WORDS)     

Arenaviruses: Cellular Response to Long-Term In Vitro Infection with Parana and Lymphocytic Choriomeningitis Viruses

Persistent infections were established in suspension cultures of BHK21/13S cells with both Parana and lymphocytic choriomeningitis viruses. Four generations after infection with either virus, more than 90% of the cells scored as infective centers, with concomitant peaks in extracellular virus yields. In both cultures the synthesis of detectable plaque-forming units (PFU) ceased about the 50th generation postinfection, and this condition was maintained until the 350th cell generation when the cultures were discontinued. The generation time of each culture was identical to that of uninfected parent controls, and at no time were cytopathic effects evident. In spite of the absence of infectivity, over 90% of the cells sampled at various times contained viral antigen demonstrable by immunofluorescence. When either of these persistently infected cell lines was substituted for normal cells in the standard plaque assay, very low efficiencies of plating were observed for homotypic and heterotypic viruses. Plaque formation by several heterologous viruses was virtually unaffected. The mechanism of homotypic plaque exclusion in both cell lines was shown to occur beyond the virion adsorption stage. The original infecting virus genome persisted in both cell lines after standard virus was no longer detectable. This was shown with the lymphocytic choriomeningitis virus-infected cells after storage in liquid nitrogen. After thawing, such cells were found to synthesize standard virus for a brief period. Although the Parana virus-infected cells did not behave this way, the growth medium from these cells would initiate PFU synthesis in normal cells within 36 hr after infection.     

Long-term persistent vesicular stomatitis virus and rabies virus infection of cells in vitro.

BHK 21 carrier cells persistently infected with VSV Indiana for over 2 years have been shedding generally very low levels of mature infectious virus or mature T particles (averaging less than one-hundredth p.f.u./cell/day) yet most cells are producing virus antigens and are resistant to homologous superinfection. However, large amounts of biologically active T particle RNP can be recovered from cytoplasmic extracts of these carrier cells even at times when they are shedding no detectable infectious virus. This recovered cytoplasmic RNP replicates (with helper B virions) to produce mature T particles, interferes strongly after DEAE dextran-facilitated uptake and, together with B virions, allows the establishment of a persistent carrier state in exposed cells. No 'provirus' DNA copies of the VSV RNA genome are detectable (less than 1/40 copy/cell or I copy per 40 cells) in carrier cells after more than 2 years of persistent infection, and all transfection attempts have failed using DNA from these VSV carriers or DNA from carrier cells persistently infected with some other negative strand RNA viruses (measles, mumps, LCM, influenza, rabies). Infectious viruses shed after more than I year from carrier cells originally infected with wild-type B virions are small plaque mutants showing a slight temperature sensitivity. Cured cell populations can be obtained from the long term VSV carrier culture by cloning in the presence or absence of antiviral antibody.