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Biomedical subjects

K Reddy

Publications and source records attributed to K Reddy.

At least 73 records · Page 4Linked to original sources
PubMed1996

Native and oxidized low density lipoproteins modulate mesangial cell apoptosis.

Hyperlipidemia has been demonstrated to contribute to hypercellularity of the mesangium in experimental animal models of glomerulosclerosis. We studied whether it also has the potential to convert a hypercellular mesangium into a hypocellular one by inducing mesangial cell (MC) apoptosis. Low density lipoprotein (LDL) enhanced (P < 0.001) mouse mesangial cell (MMC) proliferation at lower concentrations (control, 10.3 +/- 0.3 vs. LDL 100 micrograms/ml, 24.2 +/- 0.3 x 10(4) cells/ml) but augmented (P < 0.001) apoptosis at higher concentrations (control, 5.6 +/- 0.5% vs. LDL, 500 micrograms/ml 26.2 +/- 3.4% apoptotic cells/field). Oxidized (OX) LDL enhanced MMC apoptosis in concentrations of 50 to 200 micrograms/dl. There was a direct relationship between MMC apoptosis and oxidation of LDL as judged by measuring thiobarbituric acid reactive species (TBARS). Since superoxide dismutase (SOD) attenuated (P < 0.001) LDL-induced MMC apoptosis, it seems to be mediated through the generation of free radicals by mesangial cells (control, 4.3 +/- 1.5%; LDL, 200 micrograms/ml, 19.4 +/- 0.5%; LDL + SOD, 8.1 +/- 1.3% apoptotic cells/field). LDL also induced a similar effect on human mesangial cells. These studies were further confirmed by DNA fragment assays and ELISA for programmed cell death. LDL treated cells also showed enhanced mRNA expression for RSG-2, a marker for active cell death. These in vitro results provide a basis for the speculation that LDL has the potential to cause an initial hypercellular and subsequent hypocellular mesangium in the course of the development of glomerulosclerosis.

Animals↗
PubMed1996

Comparison of captopril-thiazide and enalapril-thiazide combinations in the management of mild to moderate black hypertensive patients: how important is diuretic dose and duration of action of the ACE-inhibitor?

A double-blind, randomized, parallel-group study was performed to compare the efficacy and tolerability of captopril-thiazide and enalapril-thiazide combinations. After a 3-week placebo run-in period, 47 Black patients with mild to moderate essential hypertension (mean 24-hour diastolic blood pressure (BP) > 90 mmHg and < 115 mmHg) were randomized to receive 1 of 2 combination tablets: captopril 50 mg plus hydrochlorothiazide 25 mg (CAP, n = 24) or enalapril 20 mg plus hydrochlorothiazide 12.5 mg (COR, n = 23) once daily. After 12 weeks of active treatment the mean 24-hour ambulatory BP was reduced from 152 +/- 11/99 +/- 6 to 133 +/- 13/86 +/- 7 mmHg (p < 0.005) in the CAP group and 157 +/- 15/100 +/- 6 to 141 +/- 18/90 +/- 12 in the COR group (p < 0.005). Target BP (24-hour diastolic BP < 90 mmHg) was achieved in 75% (18/24) of patients on CAP and 48% (11/23) on COR (p = n.s.). 24-hour BP load fell significantly with both CAP (from 69% to 34%, p < 0.001) and COR (from 67% to 37%, p < 0.001). Left ventricular mass index decreased by 7% with CAP and 11% with COR. Cardiac index and fractional shortening remained essentially unchanged in both groups. Both treatments were well tolerated and overall incidence of side effects was very low. It is concluded that both CAP and COR are effective, safe first-line antihypertensive choices in Black patients with mild to moderate hypertension with the former showing a trend towards greater efficacy than the latter.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1995

Effects of amlodipine on 24-hour ambulatory blood pressure profiles, electrocardiographic monitoring, and left ventricular mass and function in black patients with very severe hypertension.

In a 3-month, open-label study, 54 consecutive black patients with very severe hypertension were treated with amlodipine. Very severe hypertension was defined as an average sitting diastolic blood pressure (BP) > or = 115 mmHg and < or = 140 mmHg as a mean of 10 readings over a 30-minute period using an automatic BP measuring device and a mean 24-hour diastolic ambulatory blood pressure (ABP) > or = 110 mmHg and < or = 140 mmHg). Serial changes in 24-hour ABP and electrocardiographic monitoring, left ventricular (LV) mass index, and LV systolic function were evaluated. Mean 24-hour ABP was reduced from 181 +/- 14/119 +/- 6 to 140 +/- 15/92 +/- 9 mmHg at 3 months (P < 0.0001). Target BP (mean 24-hour diastolic ABP < 90 mmHg) was achieved in 35% of the patients. The reduction in BP was sustained for 24 hours after drug administration. Simultaneous BP measurements using the automatic BP measuring device were significantly different from the ABP measurements before and after treatment, suggesting a marked "white coat" pressor effect. At baseline, frequent or complex ventricular arrhythmias (> 30 ventricular extrasystoles per hour, ventricular couplets) were present in 2 (4%) patients, with no significant change after treatment. Left ventricular mass index regressed from 140 +/- 50 to 111 +/- 30 g/m2 at 3 months (P < 0.03); LV performance was not adversely affected. Adverse effects were few and tended to disappear during the treatment period. All of the clinical laboratory parameters tested remained unchanged. In this group of patients, treatment with amlodipine showed a marked and sustained antihypertensive action as demonstrated by 24-hour ABP monitoring, and was well tolerated and associated with LV mass regression without adverse effect on systolic cardiac function. Further, a low rate of complex ventricular arrhythmias was documented.

Adult↗
PubMed1993

A comparison of speech audiometry and pure tone audiometry in patients with secretory otitis media.

Speech audiometry was performed on 15 children with secretory otitis media pre- and post-operatively and the findings compared with the pre- and post-operative pure tone audiograms. The results showed that in 30 per cent of cases pre-operatively the speech audiogram suggested a significantly worse hearing ability than that suggested by the pure tone audiogram (PTA). Where a PTA gives a borderline threshold disproportionate parental concern should be taken seriously as the hearing ability may well be worse than the PTA suggests.

Audiometry, Pure-Tone↗
PubMed1993

4-Aminopyridine in chronic spinal cord injury: a controlled, double-blind, crossover study in eight patients.

The potassium channel blocking drug 4-aminopyridine (4-AP) was administered to eight patients with chronic spinal cord injury, in a therapeutic trial based on the ability of the drug to restore conduction of impulses in demyelinated nerve fibers. The study was performed using a randomized, double-blind, crossover design, so that each patient received the drug and a vehicle placebo on different occasions, separated by 2 weeks. Drug and placebo were delivered by infusion over 2 h. An escalating total dose from 18.0 to 33.5 mg was used over the course of the study. Subjects were evaluated neurologically before and after the infusion. Two subjects returned for a second trial after 4 months and were examined daily for 3 to 4 days following drug infusion. Side effects were consistent with previous reports. Administration of the drug was associated with significant temporary neurologic improvement in five of six patients with incomplete spinal cord injury. No effect was detected in two cases of complete paraplegia and one of two severe incomplete cases (Frankel class B). Improvements in neurologic status following drug administration included increased motor control and sensory ability below the injury, and reduction in chronic pain and spasticity. The effects persisted up to 48 h after infusion of the drug, and patients largely returned to preinfusion status by 3 days. Compared with the more rapid elimination of the drug, these prolonged neurologic effects appear to involve a secondary response and are probably not a direct expression of potassium channel blockade.

4-Aminopyridine↗
PubMed1992

Viral infection of the thymus.

We have examined infection of the thymus during congenitally acquired chronic lymphocytic choriomeningitis virus (LCMV) infection of mice, a classic model of antigen-specific T-cell tolerance. Our results show that (i) infection starts at the fetal stage and is maintained throughout adulthood, and (ii) this chronic infection of the thymus can be eliminated by transfer of virus-specific cytotoxic T lymphocytes (CTL) that infiltrate the thymus and clear all viral products from both medullary and cortical regions. Elimination of virus from the thymus results in abrogation of tolerance. During the fetal stage, the predominant cell type infected is the earliest precursor of T cells with a surface phenotype of Thy1+ CD4- CD8- J11d+. In the adult thymus, infection is confined primarily to the cortisone-resistant thymocytes present in the medullary region. The infected cells are CD4+ and J11d+. The presence of J11d, a marker usually associated with immature thymocytes, on infected single positive CD4+ "mature" thymocytes is intriguing and suggests that infection by this noncytolytic virus may affect development of T cells. There is minimal infection of the CD8+ medullary thymocytes or of the double positive (CD4+ CD8+) cells present in the cortex. Infection within the cortex is confined to the stromal cells. Interestingly, there is infection of the double negative (CD4- CD8-) thymocytes in the adult thymus, showing that even during adulthood the newly developing T cells are susceptible to infection by LCMV. Virus can be eliminated from the thymuses of these carrier mice by adoptive transfer of medullary region first and then from the thymic cortex. This result clearly shows the need to reevaluate the widely held notion that mature T cells are unable to reenter the thymus. In fact, in our experiments the donor T cells made up to 20 to 30% of the total cells in the thymus at 5 to 7 days after the transfer. The number of donor T cells declined as virus was eliminated from the thymus, and at 1 month posttransfer, the donor T cells were hardly detectable. The results of this study examining the dynamics of viral infection and clearance from the thymus, the primary site of T-cell development, have implications for understanding tolerance induction in chronic viral infections.

Aging↗
PubMed1991

Results of a recently instituted programme of thrombolytic therapy in acute lower limb ischaemia.

Twenty-eight patients with acute lower limb ischaemia received low dose intra-arterial thrombolytic therapy over a 2-year period. Eighteen patients received streptokinase and ten patients received recombinant tissue plasminogen activator (rTPA). Indications included arterial thromboemboli and graft failures. Mean ischaemic times were similar in both groups. Treatment time to achieve lysis was significantly less with rTPA (P less than 0.01). Subsequent vascular procedures, including angioplasty or reconstruction, were undertaken in 36 per cent of patients. Arterial puncture site bleeding occurred in eight (29 per cent) patients. Three (11 per cent) patients suffered rethrombosis after initial successful lysis. All rethromboses were successfully lysed with rTPA. There were two major amputations. Five (18 per cent) patients died, all lytic failures in the streptokinase treatment group. There were no cerebral haemorrhagic events and no patient died as a result of thrombolytic therapy. Good clinical outcome was obtained in nine of 18 patients treated with streptokinase and in nine of ten patients treated with rTPA. Intra-arterial thrombolysis provides effective therapy with high rates of limb salvage and a low mortality rate. This study suggests that rTPA may be a more effective agent, causing less morbidity, than streptokinase.

Acute Disease↗
PubMed1991

Complications of the transsphenoidal approach to sellar lesions.

Transsphenoidal surgery is currently performed extensively for lesions of the sella turcica. The mortality and morbidity of this surgical approach are minimal, and the results satisfactory overall. Only a few studies have addressed the complications of this approach. The authors present a retrospective study of 200 transsphenoidal procedures in 196 patients over an eleven year period. There was one death due to meningitis. Major morbidity consisted of intraventricular hemorrhage in three patients, false aneurysm of the internal carotid artery in one patient and thalamic infarction in another patient. Minor morbidity details are presented. The pathogenesis of the most serious of these complications along with possible preventive measures are discussed.

Brain Diseases↗
PubMed1991

Differentiation-related regulation of 1,25-dihydroxyvitamin D3 receptor mRNA in human leukaemia cells HL-60.

Vitamin D receptor (VDR) is a nuclear protein which mediates the physiological actions of its hormone ligand, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). While it appears that the receptor-hormone complex regulates the expression of hormone-dependent genes involved in mineral homeostasis, its role in induction of differentiation of leukaemic cells is less clear. We have studied the expression of the VDR gene in several sublines of HL-60 leukaemic cells with varying responsiveness to 1,25(OH)2D3. Sublines which rapidly differentiated to monocytic forms were shown to contain elevated steady-state levels of VDR mRNA within 1 h of exposure to high concentration of 1,25(OH)2D3. This up-regulation of the expression of VDR was not apparent in sublines in which monocytic differentiation occurred after a delay of several days. Beginning at approximately 3 h after exposure to 1,25(OH)2D3 in most cases, there was a gradual decline in VDR mRNA levels. Measurement of steady-state levels of mRNA for c-myc and c-fos showed that in sublines of HL-60 cells which respond rapidly to 1,25(OH)2D3, elevation of VDR mRNA is evident prior to the changes in proto-oncogene expression. These data are consistent with the hypothesis that a change in VDR gene expression is one of the steps that promote monocytic differentiation.

Blotting, Northern↗
PubMed1991

Selective regional chemotherapy of unresectable hepatic tumours using lipiodol.

Over a 30 month period from 1987 to 1990, selective hepatic cannulation under fluoroscopic control was performed in 57 consecutive patients with primary and secondary malignancies of the liver. Fifty-three patients were subsequently treated using intra-arterial Lipiodol emulsified with epirubicin. The tumours treated were hepatocellular carcinoma (n = 35), metastatic adenocarcinoma (n = 14), intrahepatic cholangiocarcinoma (n = 3) and leiomyosarcoma (n = 1). For hepatocellular carcinoma the cumulative survival was 38% at one year; the median survival was 12.2 months for Stage I, 6.3 months for Stage II and 0.9 months for Stage III tumours. In metastatic disease the cumulative survival was 63% at one year. These data suggest that targeted intra-arterial chemotherapy with Lipiodol-epirubicin is a useful palliative therapy for patients with Stage I and II HCC, and that a controlled trial of this treatment should be undertaken.

Adenocarcinoma↗
PubMed1991

New insecticidal metabolites from soil isolate W719.

In the course of screening soil organisms for new insecticidal metabolites, strain W719 was found to produce a group of metabolites active against the tobacco budworm Heliothis virescens. The active metabolites were purified by a combination of solvent partitioning and chromatographic steps, and the physico-chemical properties and insecticidal activity of the main components were determined. The two main components have MW's of 925 and 939, appear to belong to the macrocyclic lactam family of natural products, and possess significant insecticidal activity.

Animals↗
PubMed1990

False aneurysm of the cavernous carotid artery: a complication of transsphenoidal surgery.

Although excellent results currently are being achieved with transsphenoidal surgery, life-threatening complications may occasionally result from this approach. We present a patient with carotid injury sustained during transsphenoidal surgery, who presented 6 weeks postoperatively with a large false aneurysm in the cavernous part of the right internal carotid artery. This lesion was successfully treated by trapping. The pathogenesis of this complication is discussed and the relevant literature is reviewed.

Adenoma↗
PubMed1990

Carotid artery dissection secondary to seatbelt trauma: case report.

A postmortem report of a patient with traumatic internal carotid artery dissection, along with evidence strongly suggestive of a car seatbelt as a causative factor, is presented. In this 5-foot subject, the shoulder harness could have been high, over the anterior cervical area. The authors feel this mechanism deserves consideration as one of the important causes of traumatic carotid dissection. If supported by further studies, remedial measures in the form of changes in seatbelt design, or the use of alternate protective measures may be warranted.

Adult↗
PubMed1990

Delayed and progressive multiple suture craniosynostosis.

A considerable amount of information is available on various types of craniosynostoses. The patient exhibiting single suture synostosis that progresses to involve multiple sutures is distinctly uncommon, as is the patient exhibiting delayed synostosis involving all of the calvarial sutures. We report a group of 11 such patients with progressive and delayed holocalvarial synostosis. Most patients exhibited features of raised intracranial pressure or developmental delay, and in all patients symptoms were relieved after surgery. The diagnostic and therapeutic implications of this type of presentation in craniosynostosis are discussed.

Child↗
PubMed1990

Common epitopes of serum retinol-binding proteins: a study with monoclonal antibodies.

Monoclonal antibodies were raised against purified chicken retinol-binding protein. These were characterised extensively with respect to their ability to recognize retinol-binding proteins from different species. The monoclonal antibodies exhibited differential recognition characteristics. Though the majority presented restricted reactivities, one out of the four monoclonal antibodies studied cross-reacted with retinol-binding proteins from all species tested so far.

Animals↗
PubMed1989

Insulin-receptor gene and its expression in patients with insulin resistance.

We studied the structure of the insulin-receptor gene in normal individuals and in four unrelated patients with leprechaunism (Minn-1, Ark-1, Ark-2, Can-1) and four unrelated patients with the type A syndrome of insulin resistance, both disorders associated with genetic alterations in affinity, binding capacity, and kinase activity of the insulin receptor. Genomic cloning and Southern blot analysis indicate that the normal human insulin-receptor gene is greater than or equal to 150 kilobases long and consists of a minimum of 17 exons, 6 in the genomic region of the alpha-subunit and 11 in the region of the beta-subunit. Three of the patients, one with leprechaunism and two with type A syndrome, have decreases in insulin-receptor mRNA but on genomic blot analysis have no obvious abnormalities in the insulin-receptor gene. No distinctive pattern of restriction-fragment-length polymorphisms or evidence for major insertion or deletion mutations of the insulin-receptor gene was found in any of the patients. These data indicate that the insulin-receptor gene is greater than 35 times larger than coding regions and has a complex structure. Although leprechaunism and type A syndrome are most likely due to defects in the structure and expression of the insulin-receptor gene, they are likely to be associated with specific point mutations rather than major changes in gene structure.

Cloning, Molecular↗