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Biomedical subjects

P M Rao

Publications and source records attributed to P M Rao.

At least 19 recordsLinked to original sources
PubMed2003

Effect of PSC 833, a potent inhibitor of P-glycoprotein, on the growth of astrocytoma cells in vitro.

Malignant astrocytomas have been found to express P-glycoprotein (Pgp, mdr1 gene product). It was hypothesized that in addition to conferring multidrug resistance, Pgp is intimately associated with the development of astrocytomas. Accordingly, we studied the effect of PSC 833 (PSC, Novartis), a potent inhibitor of Pgp, on the growth of Pgp-expressing astrocytoma cells. The results showed that in all the cell lines tested, PSC (10-60 microM) inhibited the growth as well as induced cell death. Cells exposed to PSC exhibited DNA ladder characteristic of apoptosis. PSC-induced cell death could be reversed by Z-VAD-fmk, a general caspase inhibitor, indicating that PSC-induced cell death was characteristic of caspase-mediated apoptosis. These results suggest a novel therapeutic strategy in the treatment of malignant astrocytomas by inhibitors of Pgp.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

The regulation of ribonucleoside diphosphate reductase by the tumor promoter orotic acid in normal rat liver in vivo.

Our earlier studies have shown that in normal hepatocytes, orotic acid (OA) inhibits DNA synthesis induced by several growth factors in vitro and after two-thirds partial hepatectomy (PH) in vivo. As in the normal liver OA induces an imbalance in nucleotide pools (specifically, an increase in uridine nucleotides, including deoxyuridine nucleotides, and a decrease in adenosine nucleotides, including ATP) and creation of this imbalance is crucial for the mitoinhibitory effects of OA, we hypothesized that ribonucleoside diphosphate reductase (RNR), a key enzyme in DNA synthesis that is regulated by nucleotide/deoxynucleotide levels, might be one of the targets for the inhibition of DNA synthesis by OA. To test this hypothesis, we subjected male Fischer 344 rats (130-150 g) to two-thirds PH in the absence or in the presence of OA (a 300-mg tablet of OA methyl ester implanted intraperitoneally at the time of two-thirds PH). The rats were killed at different times later, and their livers were processed for analysis of levels of RNR enzyme activity, protein, and mRNA transcripts. The results obtained indicated that treatment with OA resulted in a near-100% inhibition of RNR induced by two-thirds PH in rat liver, as monitored by enzyme activity and protein level. Furthermore, this inhibition was paralleled by a decrease in the mRNA transcripts for both the M1 and M2 subunits of RNR. Nuclear run-off assays indicated that this decrease in the levels of mRNA transcripts could not be attributed to an effect on transcription. However, administration of OA 20 h after two-thirds PH, when RNR mRNA transcripts were maximally induced, resulted in increased degradation of the RNR M1 and M2 subunits. Taken together, these results indicate that OA treatment decreases RNR levels induced by two-thirds PH, at the levels of enzyme activity, protein, and mRNA transcripts, and the decreased levels of mRNA transcripts appeared to be due to increased degradation of the transcripts.

Animals↗
PubMed1999

Helical computed tomography in differentiating appendicitis and acute gynecologic conditions.

OBJECTIVE: To determine the accuracy and effect of helical computed tomography (CT) in women clinically suspected of having either appendicitis or an acute gynecologic condition. METHODS: One hundred consecutive nonpregnant women suspected of having appendicitis or an acute gynecologic condition prospectively had helical CT. Interpretations were correlated with surgical and pathologic findings (41 cases) and clinical follow-up for at least 2 months (59 cases). The accuracy for confirming or excluding both appendicitis and acute gynecologic conditions was determined. The effect on patient care was determined by comparing pre-CT plans with actual treatment. RESULTS: Thirty-two women had appendicitis, 15 had acute gynecologic conditions, 27 had other specific diagnoses, and 26 had nonspecific abdominal pain. For diagnosing appendicitis or acute gynecologic conditions, CT had 100% and 87% sensitivity, 97% and 100% specificity, 94% and 100% positive predictive value, 100% and 98% negative predictive value, and 98% and 98% accuracy, respectively. After CT was done, 36 planned hospital admissions, 25 planned hospital observations, and six planned appendectomies were deferred; six women had alternative surgical procedures on the basis of CT results. One patient had an unnecessary appendectomy on the basis of CT findings. CONCLUSION: Helical CT is an excellent imaging option for differentiating appendicitis from most acute gynecologic conditions.

Acute Disease↗
PubMed1999

Helical CT and three-dimensional CT of facial and orbital injury.

Knowledge of the regions of the face and their buttresses and knowledge of the types of facial injuries frequently encountered simplifies the diagnostic task. The indications for CT include detection of suspected fractures and preoperative planning. The cost of facial CT to the hospital has declined and is little different than the cost of plain films. CT may become the screening modality of choice depending on the cost structure at any given hospital.

Emergencies↗
PubMed1999

Helical CT of appendicitis and diverticulitis.

The clinical diagnosis of appendicitis and diverticulitis remains challenging. Clinical diagnosis alone can lead to unnecessary hospitalizations and surgeries, prolonged periods of hospital observation, and delays prior to necessary medical or surgical treatment. Helical CT combined with recently reported techniques for imaging appendicitis and diverticulitis offers rapid and accurate confirmation or exclusion of these entities as well as identification of alternative conditions that can clinically mimic them. More routine use of helical CT holds great promise for improving patient care and lowering hospital resource use in patients with clinically suspected appendicitis and diverticulitis.

Appendicitis↗
PubMed1999

Plain abdominal radiography in clinically suspected appendicitis: diagnostic yield, resource use, and comparison with CT.

This study determined the diagnostic utility and hospital resource impact of plain abdominal radiography in emergency department patients with suspected appendicitis. The authors reviewed medical records of 821 consecutive patients hospitalized for suspected appendicitis; 78% had plain abdominal radiography. Sixty-four percent had appendicitis. Radiographic findings were noted in 51% of patients with, and 47% of patients without appendicitis; no individual radiographic finding was sensitive or specific. Specific conditions were suggested in 10% of impressions; these failed to correlate with final clinical diagnoses 57% of the time. Hospital cost per abdominal radiograph was $67; cost per specific, correct radiographic diagnosis was $1,593. This is compared with $270 per appendiceal computed tomography scan (based on recent literature data). The authors conclude that plain abdominal radiographs in patients with suspected appendicitis are neither sensitive nor specific, are frequently misleading, are costly per specific and correct diagnosis, and should not be routinely obtained on patients with suspected appendicitis.

Adolescent↗
PubMed1999

CT of diverticulitis and alternative conditions.

The clinical diagnosis of diverticulitis is often uncertain and frequently incorrect. Diagnostic imaging such as with helical CT offers a rapid and accurate diagnosis of diverticulitis and its complications as well as alternative conditions. In particular, helical CT combined with contrast material administered through the colon is highly accurate and can be obtained quickly. CT signs of diverticulitis include focal inflammatory wall thickening and paracolic inflammation superimposed on diverticular disease (diverticula, muscular wall hypertrophy). Common alternative conditions that can clinically mimic diverticulitis include small bowel obstruction, primary epiploic appendagitis, acute cholecystitis, appendicitis, ileitis, ovarian cystic disease, and ureteral stone disease. Early and frequent use of diverticular CT promises to improve diagnosis and treatment of patients with clinically suspected diverticulitis.

Appendicitis↗
PubMed1999

The effect of 1/3 partial hepatectomy on the growth of glutathione S-transferase positive foci.

Our previous studies indicated that glutathione S-transferase 7-7 (GST 7-7) positive foci induced after initiation have a lower threshold towards proliferative stimuli compared with surrounding hepatocytes. This observation would predict that persistent growth stimuli of low intensity could be very effective in promoting the emergence of focal lesions. To test this possibility, the present study was designed to determine the effect of 1/3 partial hepatectomy (PH) on the incidence and growth of foci in initiated rat liver. The rationale for using a 1/3 PH was that it is known to induce a proliferative response which is less intense but more prolonged compared with that elicited by 2/3 PH. Male Fischer 344 rats (110-120 g) were initiated with diethylnitrosamine (200 mg/kg, i.p.). Three weeks later 1/3 PH (median lobe), 2/3 PH (median and left lobes) or sham operation (SH) was performed. An additional group of initiated animals had the median lobe and the left lobe of the liver removed sequentially (1/3 + 1/3 PH), 3 weeks apart. All rats were killed 8 weeks after carcinogen administration. The results indicated that the number of GST 7-7 positive foci was similar in all groups; however, the percent area occupied by foci was increased in rats receiving 2/3 PH compared with SH (0.21 +/- 0. 08 versus 0.09 +/- 0.03). Interestingly, 1/3 PH was nearly as effective as 2/3 PH in stimulating the growth of foci (percent area 0.18 +/- 0.06 versus 0.21 +/- 0.08), although the magnitude of the stimulus is only half for the former group compared with the latter; peak labeling index was 19 +/- 6 with 1/3 PH compared with 40 +/- 2 with 2/3 PH. Moreover, the maximum increase in the size of foci (percent area 0.37 +/- 0.12) was achieved when the median and left lobes were removed sequentially, three weeks apart. These results indicate that persistent growth stimuli of low intensity can be very effective in promoting the growth of focal lesions.

Animals↗
PubMed1999

Development of resistance during the early stages of experimental liver carcinogenesis.

The present study was designed to determine whether the resistant phenotype is acquired at the initiated cell stage itself or requires further exposure to a promoting regimen to express resistance. Male Fischer 344 rats were initiated with diethylnitrosamine (DENA) (200 mg/kg i.p.) and were subjected to either no further treatment or to the resistant hepatocyte (RH) model of liver tumor promotion. Six weeks later, the resistance of the focal lesions generated in these two groups to the mitoinhibitory effects of 2-acetylaminofluorene (2-AAF) was determined by subjecting the rats to two-thirds partial hepatectomy (PH) in the presence of a mitoinhibitory dose of 2-AAF (5 mg/kg i.p.) given at the time of PH. Labeling index was determined by administering multiple injections of [(3)H]thymidine. All rats were killed 48 h post-PH. While only a small percentage (23%) of the glutathione S-transferase-positive foci generated by DENA in the absence of an exogenous liver tumor promoting regimen were resistant to the mitoinhibitory effects of 2-AAF, a majority (85%) of the foci became resistant to 2-AAF following exposure to the RH model of liver tumor promotion. Further, initiated rats exposed to either 2-AAF or to CCl(4) alone, the two components of the RH model, resulted in 71% of the foci being resistant to the mitoinhibitory effects of 2-AAF. Similar patterns of results were obtained when the resistance of the foci to the mitoinhibitory effects of orotic acid, a liver tumor promoter and an inhibitor of DNA synthesis in normal hepatocytes, was monitored. These results suggest that the majority of initiated hepatocytes are not of resistant phenotype, however, they have acquired a unique ability to express resistance upon exposure to certain agents such as 2-AAF and CCl(4) or to a promoting regimen such as the RH model of liver tumor promotion.

2-Acetylaminofluorene↗
PubMed1999

Introduction of appendiceal CT: impact on negative appendectomy and appendiceal perforation rates.

UNLABELLED: OBJECTIVE To evaluate the impact of appendiceal computed tomography (CT) availability on negative appendectomy and appendiceal perforation rates. SUMMARY BACKGROUND DATA: Appendiceal CT is 98% accurate. However, its impact on negative appendectomy and appendiceal perforation rates has not been reported. METHODS: The authors reviewed the medical records of 493 consecutive patients who underwent appendectomy between 1992 and 1995, 209 consecutive patients who underwent appendectomy in 1997 (59% of whom had appendiceal CT), and 206 patients who underwent appendiceal CT in 1997 without subsequent appendectomy. RESULTS: Before appendiceal CT, 98/493 patients (20%) taken to surgery had a normal appendix. After CT availability, 15/209 patients (7%) taken to surgery had a normal appendix; 7 patients did not have CT, 5 patients had surgery despite a negative CT, and 3 patients had a false-positive CT. Negative appendectomy rates were lowered overall (20% to 7%), in men (11% to 5%), in women (35% to 11%), in boys (10% to 5%), and in girls (18% to 12%). Appendiceal perforation rates dropped from 22% to 14% after CT availability. CT excluded appendicitis in 206 patients in 1997 who avoided appendectomy and identified alternative diagnoses in 105 of these patients (51%). CONCLUSION: The availability of appendiceal CT coincided with a drop in the negative appendectomy rate from 20% to 7% in all patients, and to only 3% in patients with a positive CT. Perforation rates decreased from 22% to 14%. Appendiceal CT can be advocated in nearly all female and many male patients.

Adolescent↗
PubMed1999

Helical CT in emergency radiology.

Today, a wide range of traumatic and nontraumatic emergency conditions are quickly and accurately diagnosed with helical computed tomography (CT). Many traditional emergency imaging procedures have been replaced with newer helical CT techniques that can be performed in less time and with greater accuracy, less patient discomfort, and decreased cost. The speed of helical technology permits CT examination of seriously ill patients in the emergency department, as well as patients who might not have been taken to CT previously because of the length of the examinations of the past. Also, helical technology permits multiple, sequential CT scans to be quickly obtained in the same patient, a great advance for the multiple-trauma patient. Higher quality CT examinations result from decreased respiratory misregistration, enhanced intravenous contrast material opacification of vascular structures and parenchymal organs, greater flexibility in image reconstruction, and improved multiplanar and three-dimensional reformations. This report summarizes the role and recommended protocols for the helical CT diagnosis of thoracic aortic trauma; aortic dissection; pulmonary embolism; acute conditions of the neck soft tissues; abdominal trauma; urinary tract stones; appendicitis; diverticulitis; abdominal aortic aneurysm; fractures of the face, spine, and extremities; and acute stroke.

Abdominal Injuries↗