Metastatic adenocarcinoma presenting as an isolated ciliary body tumour.
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Adenocarcinoma↗
Biomedical subjects
S Kennedy
Publications and source records attributed to S Kennedy.
Mechanisms by which the Hawksley random zero sphygmomanometer underestimates blood pressure and produces a non-random distribution of RZ values.
Four faults are reported in the Hawksley Random Zero Sphygmomanometer (RZS). Our study is of their mechanism. (i) Compared with a mercury sphygmomanometer the RZS underestimates blood pressure (BP). We confirm this: for 240 measurements by three experienced operators in 12 patients, systolic BP was 3.4 mm Hg lower in the RZS; diastolic pressure was not underestimated. A cause of under-estimation in 89% of measurements was that mercury stuck in the manometer giving a false high reading of random zero (RZ). Tilting the RZS before reading RZ reduced under-reading by 1.6 mm Hg. A rare cause is failure of the operator to completely close the reservoir tap. (ii) Values of RZ are not randomly distributed; non-randomness is most marked in measurements made by experienced operators whose speed of measurement provides insufficient time during cuff inflation for filling of the diaphragm chamber. Smaller contributions are made by the sticking of mercury in the manometer and by a leak of air through the air bleed screw. (iii) Consecutive RZ estimates often have similar value. This has two causes: short cuff inflation time and short interval between opening the reservoir tap and spinning the thumb-wheel. (iv) An inverse relation of RZ and BP suggested by earlier work and by our own data is probably an artifact: when BP is low, measurement is quick and RZ is falsely high; when BP is high, measurement takes longer and RZ is lower. These four faults could be partly or wholly avoided by a change in the operators' technique.
Bias↗
Uterine cavity assessment prior to in vitro fertilization: comparison of transvaginal scanning, saline contrast hysterosonography and hysteroscopy.
A total of 44 patients undergoing in vitro fertilization (IVF) and requiring uterine cavity assessment agreed to have both saline contrast hysterosonography (SCHS) and hysteroscopy. SCHS was performed following a baseline transvaginal scan by injection of saline into the uterine cavity during continuous scanning. Hysteroscopy was performed with a flexible fiberscope with a 3.6-mm outer diameter; 38 of 44 women (86%) underwent both procedures. Hysteroscopy diagnosed intrauterine abnormalities in 16 women. SCHS was in complete agreement in 13 of 16 cases. As a screening test for any cavity abnormality, SCHS had a 87.5% sensitivity, 100% specificity, 100% positive predictive value and 91.6% negative predictive value. In 14 women, an abnormal uterine cavity was apparent on transvaginal scanning (TVS). However, TVS, unlike SCHS, could not (1) confidently diagnose submucosal fibroids in the presence of a uterus with multiple fibroids; (2) distinguish between a hyperplastic endometrium and a large polyp; or (3) differentiate between an arcuate and a septate uterus. In addition, ovarian pathology was diagnosed on TVS in five women: endometrioma (n = 1), complex cysts (n = 2) and polycystic ovaries (n = 2). SCHS is a simple, accurate, well-tolerated procedure that can be performed within a fertility unit, avoiding invasive and expensive diagnostic hysteroscopy. Significant findings can be treated by operative hysteroscopy prior to commencing an IVF treatment cycle.
Adult↗
Is there a genetic basis to endometriosis?
It is likely that endometriosis is a common multifactorial disease, like diabetes and asthma, caused by an interaction between multiple gene loci and the environment. Such conditions do not have a clear Mendelian pattern of inheritance. This chapter reviews the existing evidence, in human and non-human primates, that suggests there is a genetic basis to endometriosis. The environmental agents that have been implicated in the development of endometriosis are also reviewed. The identification of genetic loci conferring susceptibility to endometriosis using linkage analysis may lead to a better understanding of disease aetiology and, in time, improved therapeutic strategies and diagnostic methods.
Animals↗
Is routine diagnostic laparoscopy for infertility still justified? A pilot study assessing the use of hysterosalpingo-contrast sonography and magnetic resonance imaging.
We assessed the value of hysterosalpingo-contrast sonography (HyCoSy) and magnetic resonance imaging (MRI) as alternatives to laparoscopy and dye insufflation with or without hysteroscopy in the investigation of infertility. A total of 19 women had all three procedures, in addition, one became pregnant after HyCoSy alone. The findings were: uterine fibroids (n = 5), minimal-mild endometriosis (n = 4) and moderate-severe endometriosis (n = 3) including one case of bilateral endometriomas, endometrial polyp (n = 1), polycystic ovaries (n = 2), bilateral dermoid cysts (n = 1), haemorrhagic corpus luteal cyst (n = 1) and minimal adhesions (n = 3). At laparoscopy, 31/37 tubes were patent and there was 84% concordance with the tubal patency findings at HyCoSy. The uterine fibroids and ovarian cysts were detected using transvaginal scanning; the endometrial polyp and a congenital uterine anomaly were identified using HyCoSy. These findings were detected using MRI, but in addition the technique distinguished the dermoid cysts from the endometriomas, identified the two other cases of moderate-severe endometriosis, fibroids <2 cm (n = 2) and adenomyosis (n = 5), and interpreted the haemorrhagic corpus luteum as an endometrioma. Our data suggest that women with normal HyCoSy and MRI findings have a normal pelvis and may not need routine surgical investigation.
Adult↗
Influence of nitric oxide on luminol-enhanced chemiluminescence measured from porcine-stimulated leukocytes.
The influence of endogenous nitric oxide (NO) and NO-releasing compounds on free radical release from porcine leukocytes was investigated by luminol-enhanced chemiluminescence (CL). The direct free radical-scavenging activity of the compounds was determined by a cell-free system using xanthine plus xanthine oxidase (X + XO). The NO donor, N-(2-hydroxyethyl)nicotinumide nitrate (nicorandil), markedly inhibited CL generated by phorbol myristate acetate (PMA)-stimulated leukocytes. In addition, nicorandil and S-nitrozo-N-acetylpenicillamine (SNAP) both decreased CL generated by X + XO. Conversely, C87 3754, a NO-releasing sydnonimine, decreased free radical release from leukocytes only when preincubated with the cells and had no effects on the X + XO system. None of the NO donors inhibited peroxynitrite-generated CL. L-, but not D-, arginine inhibited PMA-activated free radical generation without affecting X + XO-induced CL. L-Canavanine, N omega-nitro-L-arginine (L-NNA), and L-nitro-arginine methyl ester (L-NAME), inhibitors of the NO pathway, augmented PMA-induced CL. However, L-canavanine, but not L-NNA and L-NAME, produced a significant inhibition of X + XO-induced CL. It is concluded that endogenous NO may play an important role in the measurement of free radicals released from porcine leukocytes, assessed by luminol-enhanced CL, and that compounds with NO-releasing properties decrease CL, possibly by interfering with free radical generation.
Animals↗
Inhibition of HIV infectivity by human saliva.
OBJECTIVE: Human saliva is known to decrease HIV infectivity in vitro. The purpose of this study was to extend these findings and to focus on the mechanism of action of these salivary factor(s). DESIGN: A number of viruses and several assay systems have been utilized to determine if the effect of submandibular saliva is directly on the virus, on the host cell, or on the virus-cell interaction. MATERIALS AND METHODS: Submandibular saliva from seronegative donors was incubated with HIV-1, other retroviruses, or unrelated viruses. Viral infectivity was monitored either by determining p24 antigen levels in peripheral blood mononuclear cells or Sup T1 cells, or using HeLa cells expressing CD4 and an HIV derived long terminal repeat linked to the beta-galactosidase gene. RESULTS: The inhibition of viral infectivity by submandibular saliva is specific for HIV-1. While inhibition increases with time of incubation of saliva with virus, pretreatment of cells with saliva does not inhibit HIV production, and saliva has only modest inhibitory effects when added to HIV-infected cells. CONCLUSIONS: It appears that the effect of submandibular saliva on decreasing the infectivity of HIV-1 is directly on the virus, rather than on the host cell.
Antiviral Agents↗
Detection of human immunodeficiency virus type 1 (HIV-1) antibody by western blotting and HIV-1 DNA by PCR in patients with AIDS.
The human immunodeficiency virus type 1 (HIV-1) Western blotting (immunoblotting) band patterns and the sensitivity of an HIV-1 DNA PCR assay were determined by testing the blood of patients with AIDS. Plasma and cell pellets processed from the peripheral blood of 199 patients with absolute CD4 cell counts of less than 200 cells per mm3 were tested by a licensed enzyme immunoassay (EIA; Abbott HIV-1) and Western blot assay (Cambridge-Biotech) for HIV-1 antibody. The Roache HIV-1 AMPLICOR DNA PCR assay was used to test cell pellets from 125 of the 199 patients for HIV-1 gag DNA sequences. All plasma samples from these 199 sequential patients were reactive for HIV-1 antibody by EIA and were positive by Western blot assay using the criteria recommended by the Centers for Disease Control and Prevention. The majority of samples (192 of 199; 96.5%) displayed at least six of nine bands characteristic of the virus by Western blotting, with the lowest number of bands characteristic of the virus displayed by any sample being three. However, 39 and 48% of all patients exhibited no bands to p17 and p55 antigens, respectively, whereas 0 to 7.5% of all patients exhibited no bands to the other antigens. HIV-1 gag DNA sequences were detected in 117 (93.6%) of 125 cell pellets processed from the peripheral blood of these same patients. All eight patients initially negative by PCR tested positive when a second pellet which had been produced from the same blood sample was tested. Despite a decrease in antibody reactivity to HIV Gag and Pol proteins, patients with advanced HIV-1 infection remained positive for HIV-1 antibody by EIA and Western blot testing. Confirmation by the HIV-1 Western blot assay still appears to be the more sensitive assay for the diagnosis of HIV-1 infection in those individuals with advanced HIV-1 infection in the United States.
Acquired Immunodeficiency Syndrome↗
A new mdr-1 encoded P-170 specific monoclonal antibody: (6/1C) on paraffin wax embedded tissue without pretreatment of sections.
AIMS: The generation and characterisation of a monoclonal antibody that specifically recognises the mdr-1 encoded protein, P-glycoprotein (P-170), on routinely processed formalin fixed, paraffin wax embedded tissue sections. METHODS: The monoclonal antibody, designated 6/1C, was produced following a combination of in vivo and in vitro immunisation regimens in Balb/c mice with a synthetic 12 amino acid peptide that corresponds to amino acids 21-32 (believed to be intracellularly located) of P-170 and has insignificant homology with the mdr-3 encoded P-170. Antibody 6/1C was characterised by western blotting and immunocytochemistry on cytospins of paired multidrug resistant or sensitive cell lines, including mdr-1 and mdr-3 transfected cells, and by immunohistochemistry on normal and malignant formalin fixed paraffin wax embedded tissue sections. RESULTS: Antibody 6/1C showed a single band at 170 kDa on western blots of multidrug resistant cell lysates and mdr-1 transfected cell lysates that was absent on similar preparations of drug sensitive cells and mdr-3 transfected cells. Immunocytochemical studies on cytospins of multidrug resistant cells and mdr-1 transfected cells revealed strong inner plasma membrane/cytoplasmic staining. Staining was negligible on drug sensitive cells and cells transfected with the mdr-3 gene. Immunohistochemical studies on formalin fixed, paraffin wax embedded normal adult kidney, liver, and breast tissue and a range of fetal tissues exhibited staining patterns of a variety of secretory surfaces consistent with documented mdr-1 specific staining. Specific staining of malignant cells in similarly treated sections of breast tumours was seen also with antibody 6/1C. Staining on paraffin wax embedded tissue with this antibody did not require any pretreatment of tissue sections. CONCLUSIONS: This new monoclonal antibody, chosen for its specificity with the mdr-1 encoded P-170 and its reactivity on routinely fixed paraffin wax embedded tissue samples without pretreatment, appears to be useful for the investigation of P-170 in archival material. It is especially useful for retrospective studies on pretreatment and post-treatment tissue sections, and could help establish when and how rapidly mdr-1 associated drug resistance develops during chemotherapeutic regimens. Immunohistochemical assessment of P-170 expression in many cancers has potential for diagnostic purposes and may influence the choice of chemotherapeutic drugs used in the treatment of refractory tumours.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Histologic, immunohistochemical, and polymerase chain reaction studies of bottlenose dolphins from the 1987-1988 United States Atlantic coast epizootic.
Tissues from 95 bottlenose dolphins (Tursiops truncatus) that died during the 1987-1988 US Atlantic coast epizootic and 11 bottlenose dolphins that died along the Atlantic coast prior to 1987 were examined histologically and immunohistochemically. Polymerase chain reaction (PCR) testing was performed on 36 of the epizootic and all of the pre-1987 cases. Epizootic cases had syncytia and rare intranuclear and intracytoplasmic inclusion bodies within lung, lymph node, and spleen. Lymphoid depletion was present in lymph node, spleen, and gut-associated lymphoid tissue of epizootic cases. Pre-1987 cases did not have these pulmonary and lymphoid lesions. A larger percentage of epizootic than pre-1987 cases had bacterial and/or fungal infections (primarily pneumonias), pulmonary and lymphoid tissue histiocytosis, mucocutaneous ulcers, and evidence of negative energy balance. Immunohistochemically, 49/95 (52%) epizootic dolphins were positive for morbilliviral antigen. Morbilliviral antigen was detected in lung, lymph node, spleen, thymus, skin, tongue, esophagus, liver, pancreas, gastrointestinal tract, urinary bladder, oviduct, and mammary gland by immunohistochemistry. PCR testing identified morbilliviral RNA in 35/36 (97%) epizootic cases tested. Neither morbilliviral antigen nor morbilliviral RNA were detected in pre-1987 cases. Histologic, immunohistochemical, and PCR results provide strong evidence that morbillivirus infection was the primary cause of the 1987-1988 bottlenose dolphin epizootic.
Animals↗
Histopathologic and ultrastructural alterations of white liver disease in sheep experimentally depleted of cobalt.
Many cobalt-deficient sheep develop liver lesions known as ovine "white liver" disease, but the etiology of these changes is controversial. It has been suggested that cofactors are required for development of liver damage in cobalt-deficient sheep. In this study, one group of lambs (n = 5) was fed a diet low in cobalt (4.5 micrograms/kg) while a group of control lambs (n = 4) received the same diet after it had been supplemented with cobalt (1000 micrograms/kg). All cobalt-depleted lambs had reduced growth rate, anorexia, lacrimation, and alopecia, and they eventually became emaciated (mean body weight at end of study: 83% of initial body weight). Plasma concentrations of bilirubin and serum activity of glutamate-oxaloacetate transferase were elevated in these animals, while plasma concentrations of vitamin B12 were reduced (less than 220 pmol/L from day 42). Fatty degeneration of the liver associated with reduced concentrations of vitamin B12 (14.5 pmol/g) was seen in these animals at necropsy at 196 days. Microscopic liver lesions included accumulation of lipid droplets and lipofuscin particles in hepatocytes, dissociation and necrosis of hepatocytes, and sparse infiltration by neutrophils, macrophages, and lymphocytes. Ultrastructural hepatocytic alterations included swelling, condensation and proliferation of mitochondria, hypertrophy of smooth endoplasmic reticulum, vesiculation and loss of arrays of rough endoplasmic reticulum, and accumulation of lipid droplets and lipofuscin granules in cytoplasm of hepatocytes. No liver lesions were seen in control lambs. The results of this study indicate that cofactors are not a prerequisite to development of hepatic damage in cobalt-deficient sheep. Reduced activities of the vitamin B12-dependent enzymes, methylmalonyl CoA mutase and methionine synthase, and lipid peroxidation are of likely pathogenetic importance in the development of the lesions.
5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
A comparative study on the use of virus and antibody detection techniques for the diagnosis of La Piedad Michoacan paramyxovirus (LPMV) infection in pigs.
La Piedad Michoacan paramyxovirus (LPMV) is newly recognized paramyxovirus that has been associated with neurologic and reproductive disorders in pigs in Mexico. To date, no comparative study of methods for the diagnosis of infection with this virus has been published. In this study, we identified tissues containing maximum virus load to optimize virus isolation procedures, and we compared this method to a rapid diagnostic test employing immunostaining of impression smears for LPMV antigens. In addition, several of the available tests for detecting LPMV antibodies were compared for their sensitivity in detecting seroconversion. Pigs used for the study of virus load in tissues and serologic studies were inoculated at 17 days of age with 10(7.00) TCID50 of LPMV. Serial blood samples were collected from selected pigs, and selected pigs were necropsied over a 14-day period. Pigs used in the investigation comparing standard virus isolation techniques to immunostaining of impression smears were inoculated at 3 days of age as described above and necropsied over an 8-day period. The results demonstrate that in the 17-day-old pigs maximum virus titers were detected in olfactory bulb at 5 days postinoculation (PI) and in midbrain at 9 days PI. In addition, the most consistent recovery of high titer virus was from tonsil (3-9 days PI) and olfactory bulb (4-9 days PI). Immunostaining of impression smears was as sensitive as virus isolation when selected tissues (lung, midbrain, olfactory bulb) were compared, with virus detected by both methods in 11/13 samples and in 1 sample each by immunostaining and virus isolation, respectively. All of the serology tests investigated detected seroconversion in pigs by 8 days PI. The identification of target organs where highest virus titers are found combined with immunofluorescent methods for the detection of LPMV antigens and a comparative study of the available serologic tests should facilitate the selection of techniques suitable for any laboratory to diagnose LPMV infection in pigs.
Animals↗
Distribution of cytopathic and noncytopathic bovine viral diarrhea virus antigens in tissues of calves following acute experimental infection.
The distribution of cytopathic and noncytopathic biotypes of bovine viral diarrhea virus (BVDV) in the tissues of colostrum-fed and colostrum-deprived calves was investigated. Colostrum-fed (group A) and colostrum-deprived (group B) calves were experimentally infected with the BVDV isolate 80/1, which contains both BVDV biotypes. Colostrum-deprived calves were also experimentally infected with a noncytopathic BVDV (group C) or with a cytopathic BVDV (group D) cloned from the 80/1 isolate. All calves were sequentially euthanized, and a wide range of tissue samples were processed for immunofluorescent and virus isolation studies. In group A, consistent immunofluorescent staining for BVDV was detected in vascular smooth muscle of numerous blood vessels in the tissues examined, mainly at 11 and 13 days postinoculation. A predominance of samples containing cytopathic BVDV was observed in the calves of this group, following virus isolation studies. Both cytopathic and noncytopathic BVDV were detected/recovered from a larger range of specimens in the calves in group B than from the calves in group A. In the calves in all the experimental groups, large amounts of BVDV antigen were detected mainly in tissue samples from the lymphoid and gastrointestinal systems, whereas only minimal amounts of BVDV were detected in the respiratory tract. Abundant noncytopathic BVDV antigen was also detected in pituitary gland and in Langerhans islets in pancreases of colostrum-deprived calves infected with the cloned noncytopathic BVDV. Noncytopathic BVDV was isolated from a wider range of tissues from calves in group C than in the colostrum-deprived calves infected with both BVDV biotypes. A cytopathic BVDV was isolated/detected in retropharyngeal, mesenteric, and abomasal lymph nodes and in thymus of 2 calves in group C. Cytopathic BVDV was detected/isolated mainly from mesenteric lymph nodes and Peyer's patches of the calves in group D.
Animals↗
Laboratory and clinical evaluation of a portable computerized peak flow meter.
A mini-Wright based peak flow meter (VMX Mini-Log), which stores the readings together with the time and date of each measurement, has recently been marketed but has not yet been evaluated. The accuracy, reproducibility, and interdevice variability of this instrument were investigated using a pneumotachograph connected in series as a standard. Flows from 100 to 700 L/min were generated by an explosive decompression chamber. The performance of this instrument was also tested in 20 normal subjects and in 20 patients with airflow obstruction. The accuracy of the instrument was expressed as the percentage of error, and reproducibility and interdevice variability were assessed using the coefficient of variation. In the laboratory evaluation, all devices recorded flow rates that were within +/-10% of the pneumotachograph readings at flows between 200 and 600 L/min. At the extreme flow rates of 100 and 700 L/min, the mean error was higher than 10%. The reproducibility of the VMX was within +/-5% at all the flows tested. The interdevice variability was less than 5% at flow rates between 200 and 700 L/min. When tested on normal subjects with PEF between 400 and 700 L/min, the VMX performed well. In patients with airflow obstruction, four devices had greater than 10% error. The largest error was observed in those patients with PEF below 200 L/min. The VMX Mini-Log peak flow meter is accurate and precise in the flow range between 200 and 600 L/min. Its performance, however, may be affected in subjects with airflow obstruction and PEF below 200 L/min.
Adolescent↗
Moclobemide versus fluoxetine in the treatment of major depressive disorder in adults.
The objective of the present study was to compare the safety and efficacy of moclobemide versus fluoxetine in adult patients with major depressive disorder. The design of the study was a multicenter, double-blind, comparative, and randomized trial. A 1- to 2-week single-blind placebo washout phase was followed by 6 weeks of double-blind treatment with moclobemide or fluoxetine. A total of 150 patients were enrolled in the study. There were 128 patients eligible to be randomized, with 66 patients receiving moclobemide and 62 patients receiving fluoxetine. At the termination of the study, patients in the moclobemide group were receiving a mean dose of 440 mg +/- 123 mg, while the mean dose in the fluoxetine group was 35 mg +/- 8 mg. No significant treatment differences were found for any of the efficacy parameters. Headache and nausea were the most frequently reported adverse events in both treatment groups. Headache and blurred vision were reported significantly more often (P < 0.05) in the fluoxetine group, whereas significantly more dry mouth was reported (P < 0.05) in the moclobemide group. These results provide supporting evidence of the comparable efficacy of moclobemide and fluoxetine and the better tolerability of moclobemide when used in the treatment of major depressive disorder.
Adult↗
The foundations of effective management of bipolar disorder.
OBJECTIVES: To understand the epidemiology and course of bipolar disorder; to outline the importance of accurate and reliable diagnosis of bipolar disorder both on a cross-sectional and longitudinal basis; and to emphasize the value of a collaborative therapeutic relationship, psychoeducation, and psychotherapy. METHODS: A brief review of relevant literature to deal with the issues of diagnosis and laying the foundations for effective treatment. RESULTS: Bipolar disorder may well be a heterogeneous group of conditions with varying forms of biphasic mood dysregulation and a changing course across a lifetime. A collaborative therapeutic relationship, psychoeducation, and psychotherapy can be the basis for effective management. CONCLUSIONS: As the concept of bipolar disorder has broadened, the condition is being identified with increasing frequency in many clinical settings. It is a relapsing and recurring condition. It is now recognized that in addition to rational pharmacotherapy, there is a need to encourage a high level of treatment adherence while providing a holistic package of interventions.
Bipolar Disorder↗
Bipolar depression: treatment options.
OBJECTIVE: To review studies on treatments for bipolar depression and make recommendations for practising clinicians treating patients with bipolar depression. METHOD: Studies that examined various treatments for bipolar depression were evaluated and rated for evidence of efficacy using Periodic Health Examination criteria. The rating for classification of recommendation for an intervention was made taking both the efficacy and the side effects into consideration. RESULTS: Mood stabilizers, cyclic antidepressants, monoamine oxidase inhibitors (MAOIs), and electroconvulsive therapy (ECT) are all effective in treating bipolar depression. Almost all antidepressant treatments with the exception of mood stabilizers have been reported to induce a manic-hypomanic switch and rapid cycling. CONCLUSIONS: Mood stabilizers, lithium in particular, are recommended as the first-line treatment. Addition of a second mood stabilizer or a cyclic antidepressant would be an appropriate next step. Newer agents such as lamotrigine offer considerable promise in treating bipolar depressed patients.
Antidepressive Agents↗
Taking "cryptogenic" out of fibrosing alveolitis.
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Cobalt↗