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Biomedical subjects

S S Fernando

Publications and source records attributed to S S Fernando.

At least 19 recordsLinked to original sources

Antibodies to hepatitis C virus in patients who have had multiple transfusions in Sri Lanka.

OBJECTIVE: To determine the prevalence of antibodies to hepatitis C virus (HCV) in patients who have had multiple transfusions in Sri Lanka. SETTING: University Medical Unit at the National Hospital, Colombo, the Cancer Institute, Maharagama, and the Lady Ridgeway Children's Hospital, Colombo. PATIENTS: One to 5 ml of blood for serology was collected from 200 multiply transfused patients (those who have received five or more blood transfusions). METHOD: The sera were tested for HCV specific antibodies using a third generation anti-HCV enzyme immuno-assay (EIA) kit. All sera giving positive or intermediate EIA results were re-tested by a commercial HCV Western blot confirmatory test. RESULTS: Of the 200 patients, 10 (5%) were repeatedly positive and confirmed by the Western blot. 33% (7/21) of haemophiliacs and 10% (3/31) of thalassaemics were positive for antibodies to HCV. Antibodies were not detected in other groups of multiply transfused patients (haemolytic disease, aplastic anemias, chronic renal failure, haematological and other malignancies). Of the 200 patients, those who have had more than 80 blood transfusions had a significantly higher prevalence of antibodies to HCV. The frequency of HCV infection was also higher among those who had received factor concentrates. CONCLUSION: 33% of haemophiliacs and 10% of thalassaemics who have received multiple transfusions were infected with HCV. These findings warrant a larger study among blood donors, and justify screening and decontamination of blood and blood products given to haemophiliacs and thalassaemics in Sri Lanka.

Blood Transfusion↗

Immunolocalization of the fodrin, E-cadherin, and beta-catenin adhesion complex in infiltrating ductal carcinoma of the breast-comparison with an in vitro model.

Fodrin, E-cadherin, and beta-catenin immunolocalization was studied in 54 cases of infiltrating ductal carcinoma of the breast and compared with an in vitro model in order to study the dynamic relationship between these components of an adhesion complex. In low-grade tumours, the staining patterns were similar for both fodrin and E-cadherin, with localization of these proteins to the cell membranes. beta-Catenin showed reduced membrane staining compared with non-neoplastic epithelium. High-grade tumours displayed strong membranous as well as cytoplasmic immunolocalization of fodrin, while E-cadherin staining was fragmented or lost from the membranes, with only occasional weak intracellular staining. beta-Catenin showed fragmented membrane staining and cytoplasmic accumulation. In addition, nuclear staining of beta-catenin was occasionally observed. In a v-src-transformed MDCK cell line, following 15min of src activation, beta-catenin began to detach from the cell membrane and localize to the cytoplasm, while fodrin and E-cadherin remained unchanged. After 30-45min of src activation, the cells lost their cuboidal shape and began to lose cell-to-cell contact. Fodrin staining remained mostly membranous while that of E-cadherin and beta-catenin was fragmented and spiky. After 60min of src activation, fodrin localized completely in the cell cytoplasm, while E-cadherin and beta-catenin were partly cytoplasmic with fragmented and spiky membranous staining. Occasionally, beta-catenin was seen in the nucleus. Both in vivo and in vitro findings clearly demonstrated a disruption of the E-cadherin/beta-catenin/fodrin/cytoskeleton linkage concomitant with the loss of cell-to-cell adhesion and change in cell shape, from epithelioid to a fibroblastoid phenotype. Membranous localization of E-cadherin showed a positive correlation with oestrogen and progesterone expression, whereas loss of membranous E-cadherin and cytoplasmic accumulation of fodrin was more often observed in high-grade carcinomas and showed a positive correlation with p53 expression.

Breast Neoplasms↗

Placental site nodules and plaques: a clinicopathological and immunohistochemical study of 25 cases with ultrastructural findings.

Placental site nodules or plaques (PSN-Ps) are nodular benign lesions of the intermediate trophoblast (IT) cells in the endometrium, endocervix, superficial myometrium or fallopian tube, occurring after a remote intrauterine pregnancy. We present a study of 25 cases of PSN-Ps These lesions occurred in patients aged 18 to 44 years. Most were discovered incidentally in endometrial curettage specimens. The specimens were received as part of clinical investigations for menorrhagia, per vaginal bleeding or pelvic pain. None of the PSN-Ps was visible grossly. Microscopically, they were mostly multiple, well-circumscribed, oval or plaque-like cellular nodules. The IT cells typically had abundant vacuolated or eosinophilic cytoplasm. The nuclei were irregular, large, hyperchromatic, often degenerate-looking and either mononucleated, multinucleated or multiclefted. Hyalinization surrounding individual or groups of IT cells, or located in the centre of the nodules, was a constant feature in all cases. The lesional cells were strongly immunoreactive to CAM 5.2, 34 beta E12, AE1/AE3, EMA and vimentin. Some cases showed focal positivity to HCG and HPL. PLAP staining was consistently negative. Ultrastructurally, the IT cells showed prominent nuclear variation in size and shape. The abundant, vacuolated cytoplasm contained some rough endoplasmic reticulum and loosely arranged filaments. This study describes the clinicopathological and immunophenotypic features of 25 cases of PSN-Ps including the ultrastructural findings of one case.

Adolescent↗

Massive ovarian oedema: 3 cases and clinical considerations.

Three cases (2 of which presented with torsion) of massive ovarian oedema occurring in young women, clinically suspected to be a neoplasm, are presented. Microscopic examination of each showed diffuse interstitial oedema and multiple cysts, some surrounded by luteinized cells. As the patients are young, we advocate conservative management with sparing of reproductive capacity, although that is not what happened with any of our 3 patients.

Adolescent↗

Effect of adenosine infusion on oxygen induced carbon dioxide retention in severe chronic obstructive pulmonary disease.

BACKGROUND: In normal subjects intravenous adenosine infusion has been shown to stimulate ventilation with a consequent fall in arterial partial pressure of carbon dioxide (Paco2), probably by an action on the carotid bodies. The objective of this study was to determine whether the increase in Paco2 seen when patients with ventilatory failure secondary to chronic obstructive pulmonary disease (COPD) are given a high concentration of oxygen to breathe might be ameliorated by an intravenous infusion of adenosine. METHODS: Eight subjects with chronic stable ventilatory failure secondary to COPD were studied. Their mean (SE) forced expiratory volume in one second (FEV1) was 0.63 (0.12) 1 with forced vital capacity (FVC) of 1.63 (0.21) 1. They received continuous intravenous infusions of saline and adenosine in random order, double blind. The infusions were administered for two minutes at 20 micrograms/kg/min, increasing in increments of 20 micrograms/kg/min every two minutes to a maximum infusion rate of 80 micrograms/kg/min adenosine (or an equivalent saline infusion rate), or until side effects supervened. The infusions were continued at that rate for five minutes, after which the fractional inspired oxygen (FIO2) was raised to 0.50 during a further 20 minutes of the infusion at that rate. Haemoglobin oxygen saturation (SaO2) and transcutaneous PCO2 (PtcCO2) were monitored throughout the procedure. Spirometric tests were performed before and after each infusion. RESULTS: Adenosine infusion was accompanied by a fall in PtcCO2 from a mean (SE) of 7.29 (0.42) kPa to 6.95 (0.48) kPa: mean difference -0.34 (95% confidence interval, -0.56 to -0.11) kPa. During saline infusion oxygen administration resulted in an increase in transcutaneous PtcCO2 from 7.35 (0.34) kPa to 7.88 (0.28) kPa: mean difference 0.53 (95% CI 0.20 to 0.85) kPa. PtcCO2 did not rise above baseline levels when oxygen was administered during the adenosine infusion. A small fall in FVC was seen following adenosine infusion. CONCLUSIONS: The increase in PtcCO2 seen when patients with stable ventilatory failure secondary to severe COPD are given a high concentration of oxygen to breathe is counteracted by a continuous intravenous infusion of adenosine.

Adenosine↗

Ventilatory sensitivity to single breaths of CO2 around the control point in man.

We used single inspiratory capacity breaths of 5, 6 or 8% CO2 in air to obtain ventilatory responses in normal subjects, with ensemble averaging of repeated runs to define stimulus and response (Protocol 1). We also compared the effect of an inspiratory capacity (IC) breath of 8% CO2 with that of two tidal volumes (TV) at the same concentration (Protocol 2). The ventilatory response was defined first as the ratio of peak changes in ventilation and end-tidal PCO2, and secondly by the ratio of their integrals. We obtained group mean values of 0.21 L min-1 mmHg-1 for the peak method and 0.80 L min-1 mmHg-1 for integrals (Protocol 1). There was no significant difference between IC and TV response values (Protocol 2) either by the peak method (0.17 vs 0.19 L min-1 mmHg-1) or by integrals (0.47 vs 0.53 L min-1 mmHg-1). A significant decrease in ventilation was seen in the second tidal volume 8% CO2 breath, even though the stimulus was unperceived by four out of five subjects. CO2 responses can be obtained from these techniques, but the necessary analysis is too cumbersome for general use. Taking a deep breath had no detectable separate effect, but CO2 in the airway may depress ventilation even at concentrations which the subject cannot detect.

Administration, Inhalation↗

Immunohistochemical detection of p53 protein expression in mammary carcinoma: a study of 80 cases.

Overexpression of p53 protein appears to be a common event in primary mammary carcinoma. This study was performed on 80 primary carcinomas of varying type and grade. Tumor p53 protein expression was detected by means of immunohistochemistry using the monoclonal antibody D07 on formalin fixed paraffin-embedded tissue sections. p53 overexpression was found in 50 (63%) of the 80 tumors. The correlation between p53 expression and high tumor grade, presence of in situ component and lymphocytic response was significant. However, no significant association was found between p53 expression and tumor size, age of the patients or tumor vascular invasion. Our study suggested that the immunohistochemical assay was a simple method of detection of mutant p53 proteins in routinely processed paraffin-embedded tissues of primary mammary carcinoma.

Adult↗

External high frequency oscillation in normal subjects and in patients with acute respiratory failure.

External high frequency oscillation was performed on 20 healthy volunteers using a cuirass-based system, the Hayek Oscillator. Five-min periods of oscillation were carried out on each subject at frequencies of 1, 2, 3, 4 and 5 Hz. Effective ventilation was measured in terms of the fall in alveolar partial pressure of carbon dioxide immediately after oscillation. The optimum frequency for oscillation was 1-3 Hz but most of the subjects were adequately ventilated over a wide range of frequencies. Thus, the Hayek Oscillator is capable of adequately ventilating normal subjects by means of chest wall oscillation. We also compared external high frequency oscillation with intermittent positive pressure ventilation in five patients with respiratory failure. Using the same inspired oxygen fraction, the external high frequency oscillation replaced intermittent positive pressure ventilation for a 30-min period. External high frequency oscillation improved oxygenation by 16% and reduced the arterial carbon dioxide by 6%. These preliminary findings suggest that normal subjects and intensive care unit patients can be adequately ventilated by means of external high frequency oscillation.

Acute Disease↗

The Hayek oscillator. Nomograms for tidal volume and minute ventilation using external high frequency oscillation.

The Hayek Oscillator is a recent development in external high frequency ventilation and is a useful mode of ventilatory support during anaesthesia, in chronic respiratory failure and weaning in intensive care. The Hayek Oscillator is new and its application is growing, as are the number of patients who have benefited from its use. However, there are no clear guidelines on how best to adjust the oscillator to achieve optimum ventilation. A simple method of predicting changes in tidal volume and minute ventilation following adjustment would make the oscillator more useful. We present nomograms for tidal volume, minute ventilation and effective alveolar ventilation when the three variables, oscillator frequency, mean chamber pressure and peak-to-trough pressure span were adjusted. The frequency-tidal volume relationship was unaffected by a mean chamber pressure of 0, -5, -10 cmH2O, but altered with changes in peak-to-trough pressure span. We have also determined the effect of increasing negative extrathoracic pressure on functional residual capacity. The relationship between tidal volume and frequency was non-linear and related to the peak-to-trough pressure span. Mean functional residual capacity significantly increased from 2.25 l (SEM 0.10) without the cuirass at rest to 2.61 l (SEM 0.14) at -10 cmH2O (p < 0.05; n = 5) and 2.47 (SEM 0.12) at -20 cmH2O of mean chamber pressure. Vital capacity was unchanged by increasing extrathoracic pressure as was total lung capacity.

Adult↗

Effects of deep breaths on subsequent ventilation in man during rest and exercise.

1. We examined the effects of twenty-four to thirty inspiratory capacity (IC), expiratory capacity (EC) and vital capacity (VC) breaths on subsequent breathing pattern in five normal subjects at rest. 2. During IC breaths and following EC and VC breaths at rest, end-tidal CO2 pressure (PET,CO2) fell by 7.5, 8.5 and 9.5 mmHg, respectively. In the group analysis significant inhibition of ventilation of 1.5 l min-1 was seen after the IC breath but not after EC or VC breaths. 3. We repeated the study with five normal subjects under conditions of higher ventilatory drive, namely 50 W exercise (one subject was common to both groups). 4. During exercise, the drop in PET,CO2 was smaller (4.0, 3.5 and 4.0 mmHg, respectively, with IC, EC and VC breaths) but ventilation was inhibited to a greater extent. Ventilatory undershoot was seen after all three types of deep breaths. 5. We propose that the expiration to residual volume in EC and VC breaths abolished the hypocapnic inhibition of ventilation at rest, possibly by a deflation reflex which was not sufficiently powerful to overcome the ventilatory undershoot during exercise. Our results also support the view that the slope of the CO2 response curve is steeper near the control point during exercise.

Adult↗

Immunohistochemical analysis of cutaneous malignant melanoma: comparison of S-100 protein, HMB-45 monoclonal antibody and NKI/C3 monoclonal antibody.

Immunohistochemical analysis was carried out on 144 formalin fixed paraffin embedded cutaneous melanomas to ascertain the value of 3 different immune markers. The sensitivity and staining patterns regarding intensity and distribution, as well as correlation to pigment content, cell type, surface ulceration and host response was noted. The stains used were monoclonal HMB-45 (Dako product No M634), NKI/C3 antibodies (Biogenex product No MU077) and polyclonal rabbit anti S-100A protein (Dako product No L1845). Of the lesions tested, 63 were malignant melanoma with an adjacent component of superficial spreading type, 61 were malignant melanoma with no adjacent component, 2 were malignant melanoma with adjacent lentigo maligna, 8 were in situ with 7 superficial spreading melanoma and one lentigo maligna (HMF) and 10 were metastatic melanoma. All 144 lesions stained for S-100 (100% sensitivity). One hundred and thirty-seven stained for NKI/C3 (95%); 132 stained for HMB-45 (92% sensitivity). S-100 was the most sensitive marker and stained tumor cells diffusely. With HMB-45 and NKI/C3, though marginally less sensitive, staining was stronger and patchy. In addition, NKI/C3 showed a tendency for peripheral (membrane) staining. HMB-45 staining was directly proportional to the pigment content, with stronger staining of radial growth phase melanoma and negative staining of those lesions where pigment content was minimal or absent. Also, with HMB-45 a decrease in staining intensity with depth or vertical growth phase was observed. There was no relationship to cell type with HMB-45 but with NKI/C3, 5 out of the 7 that failed to stain showed spindle cell differentiation.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗

Spontaneous improvement in a patient with the hepatopulmonary syndrome assessed by serial exercise tests.

A 37 year old patient with chronic active hepatitis progressing to cirrhosis presented with increasing breathlessness and was found to be hypoxic with finger clubbing. A progressive exercise study with measurement of oxygen saturation (SaO2) showed abnormally high ventilation and desaturation to 81% at 100 W. Serial studies over nearly two years showed, first, deterioration, then improvement with lower ventilation and higher saturation levels at all work loads. This could not be correlated with any change in treatment with azathioprine, prednisolone, or propranolol.

Adult↗

Isocapnic and small hypercapnic single-breath stimuli: evidence for an inhibitory inflation reflex in conscious man.

We wished to find out if a deep inspiration had any influence on subsequent breathing which was mediated by neural rather than chemical stimuli. We therefore compared the effect on ventilation of a deep isocapnic breath with that of a similar breath containing 6% CO2, and with the effect of two successive tidal volume breaths of 6% CO2. We studied five normal subjects, each of whom repeated the three manoeuvres 20 times, and we used ensemble averaging to increase the signal-to-noise ratio. The isocapnic deep inspiration was followed by a significant inhibition of ventilation in the group in the second post-stimulus breath, and in 4 of the 5 subjects in first and second post-stimulus breaths. This was due to an increase in both inspiratory and expiratory time, with a variable effect on tidal volume. A similar initial ventilatory inhibition was seen in the response to a deep breath of 6% CO2. When the isocapnic response was subtracted from the hypercapnic response, the result was similar to that observed from two tidal volume breaths of 6% CO2. We conclude that a single deep inflation of the lungs in awake man inhibits subsequent ventilation by a neural mechanism, and that this may affect the CO2 response measured by single-breath techniques using such manoeuvres.

Adult↗

Local anaesthesia for fibreoptic bronchoscopy: transcricoid injection or the "spray as you go" technique?

Local anaesthesia for fibreoptic bronchoscopy should be given by a safe technique that is not unpleasant to the patient and should provide acceptable conditions for the bronchoscopist. Single injection transcricoid local anaesthesia was compared with the "spray as you go" technique in patients having day case fibreoptic bronchoscopy. Patients were randomised to receive either 100 mg lignocaine by a single cricothyroid puncture or 240 mg lignocaine instilled through the bronchoscope under direct vision. Further doses were given by the operator to both groups as required. The 30 patients receiving transcricoid lignocaine coughed less (3.56 (SD 3.1) coughs/min) than the 32 patients receiving lignocaine through the bronchoscope (5.89 (4.8)/min) despite receiving a lower total dose of lignocaine (322 (25.9) v 451 (20.9) mg). Cricothyroid puncture was not associated with any complications and was not unpleasant for the patients.

Administration, Topical↗