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Biomedical subjects

J Kissane

Publications and source records attributed to J Kissane.

At least 19 recordsLinked to original sources
PubMed1996

A comparison of the inactive urinary kallikrein:creatinine ratio and the angiotensin sensitivity test for the prediction of pre-eclampsia.

OBJECTIVE: To determine the relation between the inactive urinary kallikrein: creatinine ratio (IUK:Cr) and the angiotensin sensitivity test (AST) at 28 weeks of gestation and to assess each as a screening test for pre-eclampsia. DESIGN: Prospective interventional study. SUBJECTS: Four hundred and fifty-nine normotensive nulliparous women recruited from hospital antenatal clinics. SETTING: John Radcliffe Maternity Hospital, Oxford, and Queen Charlotte's and Chelsea Hospital, London. INTERVENTIONS: A urine sample for IUK:Cr measurement was provided before performing the AST at 28 weeks of gestation. Those women who demonstrated increased sensitivity to angiotensin II were entered into a randomised placebo controlled trial of low dose aspirin for the prevention of pre-eclampsia (CLASP). MAIN OUTCOME MEASURES: The development of pre-eclampsia. RESULTS: The IUK:Cr ratio was significantly lower in those women who showed increased sensitivity to angiotensin II (P < 0.0001 Student's t test). The sensitivity and specificity for detecting pre-eclampsia were, respectively, 22% and 85% for the AST and 67% and 75% for the IUK:Cr. Low-dose aspirin (60 mg) had no effect on the pregnancy outcome. CONCLUSION: There appears to be some relation between the IUK:Cr and AST tests in pregnancy. However, in this population, the IUK:Cr ratio was a better screening test for pre-eclampsia than the AST, but overall neither test was a powerful predictor for the syndrome.

Angiotensin II↗
PubMed1995

The Ivemark syndrome: prenatal diagnosis of an uncommon cystic renal lesion with heterogeneous associations.

Renal dysplasia has been reported in association with a number of anatomical abnormalities, including pancreatic dysgenesis and hepatic anomalies. The combination of renal, hepatic, and pancreatic dysplasia (RHPD), also known as Ivemark syndrome, is rare and uniformly fatal. We report here the gross and histological findings in 4 cases of combined RHPD, 2 of which were detected by prenatal ultrasonography. Evaluation of these 4 and the other 20 reported cases shows that combined RHPD has considerable variability in the histological findings and in organ involvement. In addition, nearly half were associated with anomalies in other organ systems, and 11 of the 24 were familial. In this study, ultrasonographic and histological abnormalities were seen as early as 18.5 weeks gestation in 1 case.

Abnormalities, Multiple↗
PubMed1995

The angiotensin sensitivity test and low-dose aspirin are ineffective methods to predict and prevent hypertensive disorders in nulliparous pregnancy.

OBJECTIVE: Our purpose was to assess the efficiency of the angiotensin sensitivity test as a predictive test for preeclampsia and the effectiveness of low-dose aspirin to prevent preeclampsia when commenced at 28 weeks' gestation in angiotensin II-sensitive women. STUDY DESIGN: A total of 495 healthy nulliparous women underwent the angiotensin sensitivity test at 28 weeks' gestation. The angiotensin II-sensitive women were randomized to 60 mg of aspirin or placebo as a subset of a large multicenter, randomized, controlled trial of low-dose aspirin therapy in pregnancy. Assessment of the efficiency of the angiotensin sensitivity test and low-dose aspirin in pregnancy was performed after detailed review of case notes after delivery. The Oxford definition of preeclampsia was used. This includes women without proteinuria but requires blood pressure increments that have been validated to bias the selection to primigravid women. RESULTS: Five women had proteinuric preeclampsia in the angiotensin II-sensitive group randomized to aspirin compared with none in the group randomized to placebo. Overall, 11 (25%) of the women randomized to aspirin had preeclampsia compared with four (11%) randomized to placebo (p < 0.05, not significant). The positive and negative predictive values for the angiotensin sensitivity test were 19% and 87%, respectively. CONCLUSION: The angiotensin sensitivity test is not an effective screening test for preeclampsia, and low-dose aspirin does not prevent preeclampsia when commenced at 28 weeks' gestation in angiotensin II-sensitive women.

Angiotensin II↗
PubMed1995

Acute inflammation is the harbinger of glomerulosclerosis in anti-glomerular basement membrane nephritis.

The degree of glomerular inflammation and injury during immune-mediated glomerulonephritis is felt to be critical to the eventual development of glomerulosclerosis, although the relative contributions of acute and chronic inflammation are uncertain. By grading the initial dose of antibody in accelerated anti-glomerular basement membrane nephritis, we observed that only animals with the most substantial acute inflammation (in terms of neutrophil influx and acute proteinuria) developed sustained proteinuria followed by an increase in serum creatinine and evidence of severe glomerulosclerosis. Chronic inflammation (i.e., glomerular macrophage influx and evidence of glomerular cell proliferation), in contrast, was evident without the development of glomerulosclerosis. Decreasing the degree of acute inflammation during severe nephritis by complement depletion diminished both the initial and sustained proteinuria and the influx of neutrophils, prevented the terminal increase in serum creatinine, and attenuated the evolution of glomerulosclerosis. Complement depletion, however, did not affect peak proteinuria, macrophage influx, or glomerular cell proliferation. Regression analysis of the entire data set demonstrated that acute (day 1) proteinuria was predictive of the eventual histopathological index, more so than chronic (day 7) proteinuria. To recapitulate, glomerulosclerosis following antiglomerular basement membrane nephritis appears to be substantially dependent on the degree of acute inflammatory injury.

Animals↗
PubMed1994

Hepatocyte growth factor accelerates recovery from acute ischemic renal injury in rats.

Effects of hepatocyte growth factor (HGF) administration were examined in a model of acute ischemic renal injury induced by bilateral renal artery occlusion in rats. Compared with rats administered vehicle, rats administered 20 micrograms HGF subcutaneously 30 min postischemia had significantly lower serum creatinine and blood urea nitrogen levels over the course of 7 days postocclusion, enhanced insulin clearances measured on day 2 postocclusion, reduced mortality, and much less injury evident by examination of kidney histologies 7 days postinjury. The tubular regeneration that occurred postischemic injury was reflected by increased incorporation of 5-bromo-2'-deoxyuridine (BrdU) in cortical tubular epithelium compared with incorporation in kidneys from noninjured rats. HGF enhanced BrdU incorporation compared with vehicle, indicating enhanced mitogenesis. The weight loss that occurs postischemic injury was not ameliorated by the dose of HGF we employed. We conclude that administration of HGF postischemic injury to rats stimulates the recovery of normal kidney function and the regeneration of proximal tubular epithelium.

Animals↗
PubMed1994

Rat models for clinical use of insulin-like growth factor I in acute renal failure.

Insulin-like growth factor I (IGF-I) improves kidney function and histopathology, when given within a short time (0.5 or 5 h) after an ischemic renal insult in rats. To examine the effects of IGF-I at times that would be more applicable if it were to be used as a therapeutic agent for acute renal failure in humans, we administered IGF-I to rats 24 h after ischemic injury or prior to the induction of injury (pretreatment). In rats that received IGF-I 24 h postischemia, serum creatinine and blood urea nitrogen (BUN) values were significantly lower during the subsequent 6 days than in vehicle-treated rats, and incorporation of 5-bromo-2'-deoxyuridine into tubular cells of the regenerating cortex, measured 48 h postischemia, was enhanced. When examined 7 days postinjury, kidneys from rats that received IGF-I 24 h postischemia were improved in histopathological appearance compared with kidneys from vehicle-treated animals. Whereas creatinine and BUN values were elevated above baseline in both vehicle and IGF-I-pretreated groups, recovery of normal renal function was accelerated by pretreatment with IGF-I. In addition, although we could detect no differences in histopathology at 24 h postinjury, IGF-I pretreatment resulted in more normal renal histology at 7 days postischemic injury and reduced weight loss after injury. Our data show that IGF-I hastens recovery and accelerates regeneration or repair of damaged epithelia following acute renal failure in rats when administered either 24 h postinjury or prior to induction of acute renal failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1993

Validation of the SpaceLabs 90207 ambulatory blood pressure monitor for use in pregnancy.

OBJECTIVE: To determine the accuracy of the SpaceLabs 90207 ambulatory blood pressure monitor in pregnant women. DESIGN: Prospective observational study. SETTING: Queen Charlotte's and Chelsea Hospital for Women. SUBJECTS: One hundred and twenty-two pregnant women from the antenatal population of Queen Charlotte's Hospital. METHODS: Evaluation was carried out according to the British Hypertension Society (BHS) Protocol. RESULTS: The mean difference between observer and device for systolic blood pressure was 3 (SD 4) mmHg. For diastolic blood pressure the difference was 5 (SD 6) mmHg for Phase IV (muffling of Korotkoff sound), and 4 (SD 4) mmHg for Phase V (disappearance of Korotkoff sound). According to the BHS grading criteria, the device reached a B grading for systolic blood pressure. B grading was also reached for diastolic blood pressure (Phase V) but grade C for diastolic blood pressure (Phase IV). The accuracy criteria stipulated by the Association for the Advancement of Medical Instrumentation (AAMI) were also met for both systolic and diastolic blood pressure. CONCLUSION: The SpaceLabs 90207, when compared with trained observers, is accurate in determining both systolic and diastolic blood pressure for clinical purposes, as judged by the BHS Protocol in pregnancy.

Blood Pressure↗
PubMed1993

Second trimester ambulatory blood pressure in nulliparous pregnancy: a useful screening test for pre-eclampsia?

OBJECTIVE: To assess the effectiveness of second trimester 24-hour ambulatory blood pressure measurement as a screening test for pre-eclampsia. DESIGN: Prospective interventional study. SETTING: John Radcliffe Maternity Hospital, Oxford, and Queen Charlotte's and Chelsea Hospital, London. SUBJECTS: One hundred and sixty-two normotensive nulliparous women recruited at hospital booking clinics. INTERVENTION: Ambulatory blood pressure was measured at 18 and 28 weeks gestation using the TM2420 monitor. MAIN OUTCOME MEASURE: The development of pre-eclampsia. RESULTS: Awake systolic and mean arterial pressures were significantly increased (P < 0.02) at 18 weeks in those who later developed pre-eclampsia. Those differences were more apparent at 28 weeks at which time the diastolic pressure was also increased (P < 0.01). At both stages of gestation the higher readings were sustained during sleep so that the awake-sleep differences were similar in relation to each outcome. The group with incipient pre-eclampsia had a significantly faster heart rate at both 18 and 28 weeks (P < 0.002) The sensitivity in predicting pre-eclampsia for a mean arterial pressure of 85 mmHg or greater at 28 weeks was 65%, with a positive predictive value of 31%. The sensitivity and positive predictive value for a test combining a mean arterial pressure of 85 mmHg or greater and a heart rate of 90 bpm or greater were 53% and 45%, respectively. CONCLUSION: Although second trimester ambulatory blood pressure is significantly increased in women who later develop pre-eclampsia, the predictive values for blood pressure alone are low. The efficiency of the test is increased by combining the awake ambulatory heart rate and blood pressure measurement together. If an effective method for preventing pre-eclampsia becomes available (commencing at 28 weeks gestation), then awake ambulatory blood pressure and heart rate may have some clinical value as a screening test.

Adolescent↗
PubMed1993

L-arginine administration prevents glomerular hyperfiltration and decreases proteinuria in diabetic rats.

The effect(s) of L-arginine administration on the renal function of rats with untreated diabetes mellitus was examined. Rats received streptozotocin (N = 11) or vehicle (N = 12): Group 1 (normal rats, N = 6) drank tap water; Group 2 (normal rats, N = 6) drank tap water containing 1% L-arginine; Group 3 (diabetic rats, N = 5) drank tap water; and Group 4 (diabetic rats, N = 6) drank tap water with 1% L-arginine. Rats were fed a standard rat chow diet (22.8% protein, 142% L-arginine) with free access to food and water for 14 wk. Diabetic rats gained less weight, had significantly lower plasma levels of albumin and L-arginine, and had greater values for 24-h urine volumes and urine excretion of glucose, protein, urea, creatinine, nitrate, and nitrite than control rats. Diabetic rats given L-arginine (Group 4) had significantly lower protein and cGMP excretion in the urine than did rats of Group 3. The administration of L-arginine did not affect the plasma levels of glucose or L-arginine in Groups 2 or 4 compared with those of their respective controls. Group 3 had significantly higher values for GFR than did the other three groups of rats, but values for effective RPF, mean arterial pressure, hematocrit, and renal vascular resistance were not significantly different between Groups 3 and 4. There was no significant difference in glomerular morphology among the four groups of rats as determined by light microscopy, and both groups of diabetic rats exhibited the Armanni-Ebstein lesion in their tubules.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Insulin-like growth factor I accelerates recovery from ischemic acute tubular necrosis in the rat.

The effects of administering insulin-like growth factor I (IGF-I) were examined in a model of ischemic acute tubular necrosis in rats. Injury was induced by 75 min of bilateral renal artery occlusion. Compared to rats administered vehicle, rats administered IGF-I (100 micrograms/day via continuous subcutaneous infusion) had significantly lower serum creatinine and blood urea nitrogen levels over the course of 7 days postocclusion. Glomerular filtration rate as determined by inulin clearance was examined on day 2 postocclusion and was significantly increased in IGF-I-treated animals (0.16 +/- 0.02 ml per min per 100 g of body weight) compared to vehicle-treated controls (0.08 +/- 0.02 ml per min per 100 g of body weight). The weight loss that occurred during the course of acute tubular necrosis was ameliorated by IGF-I. Mortality was reduced from 36.7% in vehicle-treated rats to 7.1% in rats administered IGF-I. Histologically, there was much less renal injury evident at day 7 postocclusion in the IGF-I-treated rats compared to vehicle-treated controls. In contrast, growth hormone (200 micrograms administered subcutaneously for 4 days) did not affect recovery of renal function or reduce mortality postreperfusion. This report demonstrates a beneficial effect of IGF-I administration in the setting of acute tubular necrosis. Several properties of IGF-I render it a pharmacological agent with excellent potential for treatment of this condition in humans.

Animals↗
PubMed1990

Ewing's sarcoma metastatic at diagnosis. Results and comparisons of two intergroup Ewing's sarcoma studies.

Two Pediatric Intergroup Ewing's Sarcoma studies of patients with metastatic disease (IESS-MD) have used multimodal therapy consisting of intensive combination chemotherapy and radiation therapy (XRT) to areas of gross disease detected at the time of diagnosis. In IESS-MD-I, conducted from 1975 to 1977, 53 eligible patients were entered and received the chemotherapeutic agents vincristine, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), cyclophosphamide, and dactinomycin with concomitant XRT (VACA + XRT). In IESS-MD-II, conducted from 1980 to 1983, 69 eligible patients were entered and received 5-fluorouracil (5FU) in addition to the chemotherapeutic agents of IESS-MD-I; initial intensive chemotherapy was given and XRT was delayed until week 10 (VACA + 5FU, delayed XRT). The best response rate (complete and partial remissions combined) was 73% in IESS-MD-I and 70% in IESS-MD-II, so there was no statistical evidence of a difference in response rates (P = 0.62). The length of best response also was similar between studies (P = 0.79), with approximately 30% of the patients on both studies remaining in remission at 3 years. The percentage of patients surviving 5 years or more was 30 on the first study and 28 on the second study (P = 0.49). The major sites of relapse after a response were lung and bone, each occurring with nearly equal frequency. The age of the patient was related to both best response rate and survival: patients 10 years of age or younger had substantially higher response and survival rates than patients 11 years of age or older. The favorable prognosis for younger patients might be explained by a more favorable distribution of primary sites at diagnosis; 39% of patients 10 years of age or younger had rib primary sites, compared with only 16% for patients older than 10 years of age (P = 0.05). The frequency of life-threatening toxicity was substantially higher in IESS-MD-I (30%) than in IESS-MD-II (9%), but the frequency of fatal toxicity was similar (6% to 7%). Fatal complications included Adriamycin-induced cardiomyopathy, Pneumocystis carinii pneumonia, unspecified pneumonitis, and sepsis. The most common toxicity and complications were leukopenia and infections.

Adolescent↗
PubMed1990

A high cholesterol diet ameliorates renal tubular lesions in diabetic rats.

These studies examine the effect of cholesterol feeding in normal rats and in rats with streptozotocin-induced diabetes mellitus. Four groups were studied: normal rats fed either a standard rat chow or a standard rat chow supplemented with cholesterol and diabetic rats fed standard chow or standard chow plus cholesterol. Diabetic rats fed a standard diet excreted more creatinine and urea in the urine, had higher levels of blood urea nitrogen, and lower serum albumin levels than rats fed standard diet plus cholesterol. Blood glucose levels were similar in the two groups; however, diabetic rats given cholesterol had a greater body weight at the end of the study than diabetic rats eating standard chow. Urine volumes and sodium and potassium excretion in the urine were greater in diabetic rats fed a standard diet than in those fed a high cholesterol diet. Diabetic rats fed a standard diet had distinctive renal lesions characterized by swelling of tubular epithelial cells with clearing of cytoplasm. The nephron segments involved by this striking vacuolar change were the distal convoluted tubule and the thick limbs of Henle's loop. These lesions were identical to those described by Armanni-Ebstein in severely glycosuric patients. These lesions were not observed in any of the animals of the other three groups (including diabetic rats fed a high cholesterol diet). Glomeruli were normal in animals of all groups. Thus, cholesterol administration prevents the development of the Armanni-Ebstein lesions in diabetic rats despite persistent hyperglycemia. The mechanism by which cholesterol administration prevents the accumulation of glycogen in distal tubule cells has not been elucidated. It is suggested that glycogen accumulation in distal tubular segments may explain the greater urine volumes, natriuresis, kaliuresis, and proteinuria observed in diabetic animals fed a standard diet when compared with rats fed the same diet plus cholesterol.

Animals↗
PubMed1985

Local recurrence, rate and sites of metastases, and time to relapse as a function of treatment regimen, size of primary and surgical history in 62 patients presenting with non-metastatic Ewing's sarcoma of the pelvic bones.

This report reviews the experience of 62 patients who presented between 1972 and 1978 with non-metastatic Ewing's sarcoma of the pelvis and were entered on IESS I. Seventeen patients (27%) developed a local recurrence, 38 patients (61%) demonstrated metastases and 21 (34%) neither. In the dose range 4000 rad to 6000 rad no dose response could be detected for local control of tumor. Forty-six patients (74%) had a biopsy or exploratory surgery only, 5 patients (8%) had an incomplete resection and 11 patients (18%) had a complete resection of their tumor. In the 46 patients having a biopsy only, 13 developed a local recurrence (28%) as compared to 2 of 11 patients undergoing a complete resection (18%). The most common sites for metastases were lung in 19 patients (31%) and bone in 23 patients (37%). No significant difference was noted in the frequency of overall metastases or metastases to any site between those patients receiving one of the three treatment regimens used in IESS I: VAC and Adriamycin (regimen I), VAC alone (regimen II) and VAC plus bilateral pulmonary irradiation (regimen III). At a median follow-up of 135 weeks no significant difference in median survival could be detected in patients with pelvic primaries between regimens I, II and III. The mean diameter of the pelvic primaries was comparable to the nonpelvic, however, one half of the pelvic cases were in the range 10-15 cm. The median time to relapse of the 241 non-pelvic patients on IESS I was 222 weeks as contrasted with the median time to relapse of 92 weeks in the 62 pelvic patients on the same study (p = 0.002). The possible reasons for the poor prognosis of pelvic primary patients are discussed together with treatment policies that might improve the survival of this group of patients.

Adolescent↗
PubMed1983

Primary Ewing's sarcoma of the ribs. A report from the intergroup Ewing's sarcoma study.

Thirty-six patients with primary Ewing's sarcoma of the ribs have been reviewed. Of these, 21 had clinically localized disease at diagnosis and were entered on protocol IESS 7299, eight had regional and seven metastatic disease at diagnosis and were entered on protocol 7450. The 21 with localized disease were treated with surgical excision or biopsy, followed by local radiotherapy (in all but one patient) and randomization to one of three chemotherapy regimens. Eleven patients (52%) remain disease-free for periods ranging from 18 to 64 months, respectively. Seven of eight patients who underwent complete surgical excision of the primary lesion remain disease-free, compared with four of 12 (excluding one patient who died disease-free) who remain disease-free after partial excision or biopsy. However, analysis of size of tumor at diagnosis reveals that smaller primary tumors have a better prognosis irrespective of extent of surgery. Protocol IESS 7450, consisted of radiotherapy to all areas of known disease and four drug chemotherapy. Four (50%) with regional disease but none with metastatic disease have remained alive and continuously disease-free. It is concluded that an aggressive approach to Ewing's sarcoma of the ribs is justified by the results, as even regional disease may be curable. The apparent prognostic advantage for those patients undergoing surgical excision may be explained by patient selection.

Adolescent↗
PubMed1981

Radiotherapy and combination chemotherapy in advanced Ewing's Sarcoma-Intergroup study.

Forty-four patients with metastatic (36 patients) and advanced regional (eight patients) Ewing's sarcoma were treated on a protocol employing intensive combination chemotherapy and radiotherapy to all sites of overt disease (primary site and metastatic sites). Thirty-one patients achieved a complete remission, eight achieved a partial remission, and five patients did not respond to treatment. Of the 31 patients who achieved a complete remission (12 had metastases and six had regional spread), 18 remained disease-free with a median follow-up of 34 months, while recurrences occurred in nine patients. Four patients died of complications of treatment. Although late relapses can still be expected, it appears that intensive multimodal management in metastatic Ewing's sarcoma can produce prolonged disease-free survival and possibly cure in a significant percentage of patients.

Adolescent↗
PubMed1981

Multimodal therapy for the management of primary, nonmetastatic Ewing's sarcoma of bone: an Intergroup Study.

A randomized study of 264 children and adults with previously untreated localized Ewing's sarcoma of bone was undertaken between 1973 and 1978 by 83 institutions of three national study groups: Children's Cancer Study Group, Southwest Oncology Group, and Cancer and Leukemia Group B. The Intergroup Study was designed to determine if the addition of adriamycin (ADR) or bilateral pulmonary radiotherapy (RT) to vincristine, dactinomycin, and cyclophosphamide (VAC therapy) would improve survival and reduce local recurrences and metastases. All patients received RT to the primary lesion, and the survival rate after 3 years was 65%. The most effective treatment regimen was VAC plus ADR; 74% of the patients were free of disease at 2 years. The lengths of disease-free status and survival of patients treated with VAC plus ADR or VAC plus RT did not differ. However, both regimens were significantly superior to treatment with VAC alone. The addition of ADR or bilateral pulmonary RT to VAC was highly advantageous to patients with nonpelvic primaries. Bone and lung were the major sites of distant relapse, but the addition of bilateral pulmonary RT showed no advantage over that of ADR in reducing the occurrence of lung metastases. These recent results should eliminate some of the pessimism that has accompanied a diagnosis of Ewing's sarcoma, although distant metastases continued to be a major reason for failure in the control of this tumor. Survival of these patients can be improved through well-controlled clinical trials designed to determine optimal adjuvant chemotherapy and treatment of the primary lesion.

Adolescent↗