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Biomedical subjects

J T Mullen

Publications and source records attributed to J T Mullen.

At least 19 recordsLinked to original sources
PubMed2001

Multimodality therapy with a replication-conditional herpes simplex virus 1 mutant that expresses yeast cytosine deaminase for intratumoral conversion of 5-fluorocytosine to 5-fluorouracil.

Infection of tumor cells by herpes simplex virus 1 (HSV-1) results in cell destruction and production of progeny virion in a process referred to as viral oncolysis. In this study, an HSV-1 mutant (HSV1yCD) was engineered such that the viral ribonucleotide reductase gene is disrupted by sequences encoding yeast cytosine deaminase, which efficiently metabolizes the prodrug 5-fluorocytosine (5-FC) to 5-fluorouracil (5-FU). HSV1yCD-infected cells convert 5-FC to 5-FU, which enhances cytotoxicity without significantly reducing viral replication and oncolysis. Oncolysis by a replicating HSV-1 mutant combined with therapeutic transgene delivery represents a new paradigm; HSV1yCD-infected cells are destroyed by viral replication, and uninfected cells are subjected to bystander killing from both progeny virion and extracellular diffusion of 5-FU. In contrast, HSV1yCD-mediated bioactivation of another prodrug, ganciclovir, impairs viral replication. HSV1yCD administered into the portal venous system replicates preferentially in liver metastases rather than normal liver. The anti-neoplastic activity of HSV1yCD combined with systemic 5-FC administration is greater than that achieved with HSV-1 replication alone. Combination oncolysis and prodrug bioactivation leads to significant prolongation of survival in mice with diffuse liver metastases.

Animals↗
PubMed2000

Oncolysis of diffuse hepatocellular carcinoma by intravascular administration of a replication-competent, genetically engineered herpesvirus.

Herpes simplex virus type 1 (HSV-1) replication within tumors can mediate tumor regression (oncolysis). The genetically engineered, HSV-1 mutant rRp450 does not express viral ribonucleotide reductase and is therefore replication conditional. During the course of infection, rRp450 expresses the cytochrome P450 transgene and HSV-1 thymidine kinase gene, thereby enabling it to bioactivate the prodrugs cyclophosphamide and ganciclovir, respectively. rRp450 replication in hepatocellular carcinoma (HCC) cells is cytotoxic and liberates progeny virion that infect adjacent tumor cells. rRp450-mediated oncolysis is enhanced in the presence of cyclophosphamide, whereas it is inhibited in the presence of ganciclovir. As a consequence of defective viral ribonucleotide reductase expression, the yield of rRp450 progeny virions from infection of HCC cells is 3 to 4 log orders greater than that from infection of normal hepatocytes. This is associated with dramatic tumor reduction of diffuse HCC after a single intravascular administration of rRp450. rRp450 holds the promise of the dual therapeutic benefit of selective oncolysis and P450 transgene delivery.

Animals↗
PubMed2000

Validity of the pain anxiety symptoms scale (PASS): prediction of physical capacity variables.

Anxious responses to pain may lead to avoidance of behavior expected to produce pain. McCracken et al. (1992) developed the Pain Anxiety Symptoms Scale (PASS) to assess anxiety related specifically to pain. Efforts to validate the scale, however, have been confined mostly to examining associations between the PASS and other self-report instruments. This study tested whether PASS scores were related to behavioral performance variables recorded by therapists during a physical capacity evaluation. Participants were 98 male patients with persistent pain referred to two industrial rehabilitation centers. PASS scores were correlated negatively with amount of weight lifted and carried, and results of hierarchical regressions showed that PASS scores accounted for additional variance in these variables when measures of trait anxiety, depression and pain severity were controlled. However, we did not replicate the findings of McCracken et al. (1992) that PASS scores accounted for variance in self-reported disability with trait anxiety, depression or pain severity controlled. Results extend the validity of the PASS and are consistent with models of fear of pain: patients with high PASS scores may avoid potentially painful physical exertion to reduce their fear.

Adult↗
PubMed1993

Amelioration of nifedipine poisoning associated with glucagon therapy.

Glucagon relieves calcium channel blocker-induced hypotension in animal studies. There are no published case reports of glucagon relieving hypotension in patients with calcium channel blocker poisoning. We describe a patient who developed hypotension after ingestion of 900 mg nifedipine. Therapy with IV lactated Ringer's solution and calcium chloride alone did not relieve his hypotension. However, hypotension rapidly resolved after the addition of IV glucagon therapy. This is the first case report of glucagon therapy at least temporally associated with relief of hypotension in a patient with calcium channel blocker poisoning. More research is needed to determine the appropriate role for glucagon in treating patients with calcium channel blocker poisoning.

Adult↗
PubMed1990

Potassium effects on blood pressure: is the conjugate anion important?

Potassium salts, often in the form of KCl, have had variable hypotensive effects in experimental animals and man. The chloride anion has recently been implicated as the hypertensive agent in salt-sensitive hypertension. We therefore hypothesized that non-chloride salts of potassium would have superior hypotensive effects to KCl. In randomized, double-blind fashion, we administered placebo, KCl (75 mmol/day) or potassium citrate (75 mmol/day) to 24 normotensive adult males. In these subjects, neither KCl nor potassium citrate affected blood pressure, despite urinary verification of potassium supplement intake. Thus, in these experimental circumstances, neither potassium nor its conjugate anion were of importance in lowering blood pressure.

Adult↗
PubMed1990

Prospective evaluation of the role of fine-needle aspiration biopsy in the diagnosis and management of patients with palpable solid breast lesions.

To evaluate the role of fine-needle aspiration biopsy (FNAB) in the diagnosis and management of patients with palpable, solid and suspicious breast lesions, a total of 107 FNABs were performed on 98 patients under the prospective FNAB protocol. Eight-four FNABs were positive for breast carcinomas; of these 84 positive FNABs, 80 underwent mastectomy without open biopsy or frozen section. Our data showed a sensitivity of 95 per cent and a specificity of 100 per cent for diagnosis of breast malignancies on these patients. We concluded that FNAB is a simple, reliable, and cost-effective diagnostic procedure for patients with palpable breast carcinomas.

Algorithms↗
PubMed1982

Blunt transection of the pancrease treated by distal pancreatectomy, splenic salvage and hyperalimentation. Four cases and review of the literature.

The increasing awareness among surgeons of overwhelming postsplenectomy sepsis has led to new and innovative procedures to save the spleen. In pancreatic transection injuries (Type II)26 the classical treatment has been distal pancreatectomy and splenectomy. The opportunity to treat several patients with pancreatic transections sustained during blunt abdominal trauma lead to the review of the literature on the subject. Particular attention was paid to treatment of these injuries during distal pancreatectomy with splenic salvage, appropriate drainage, and hyperalimentation. Associated complications were likewise investigated and reviewed.

Adolescent↗
PubMed1978

Squamous cell carcinoma of the foot.

The need for considering squamous cell carcinoma when diagnosing foot lesions is stressed in these two cases. Early diagnosis and treatment are the hallmarks of proper patient management.

Adult↗
PubMed1977

Bowel perforation with candidiasis.

Spontaneous multiple jejunal perforations developed in a relatively normal patient. Candida albicans was cultured from a biopsy specimen of an area of perforation and from peritoneal fluid. Yeasts and pseudohyphae were seen deep within the necrotic mucosa. Serial determinations of precipitating and agglutinating antibodies support the diagnosis of invasive candidiasis causing this unusual presentation.

Adult↗
PubMed1977

Routine upper gastrointestinal examinational examination in preoperative cholecystectomy patients.

The charts of 663 patients who had cholecystectomy were reviewed to determine the usefulness of preoperative radiologic examination of the upper gastrointestinal tract. In 14% of the patients a positive finding was reported. However, slightly less than half of these findings were confirmed at surgery. Only 2.9% of the patients had a procedure in addition to cholecystectomy. It is felt that routine examination of the upper GI tract is not indicated in the preoperative evaluation of patients with gallbladder disease unless the clinical history is equivocal and one suspects coincidental disease.

Adolescent↗
PubMed1977

Preoperative diagnosis of rectal bleeding in an adult using a radioisotope scan.

A 22-year-old man with burning pain in the lower abdomen and rectal bleeding had a sodium pertechnetate Tc 99m scan. The scan showed an area of uptake in the right lower quadrant which at operation was found to be a Meckel's diverticulum. The ability of ectopic gastric mucosa within a Meckel's diverticulum to concentrate sodium pertechnetate Tc 99 m allows for this noninvasive diagnosis of some types of rectal bleeding, especially when the cause has escaped detection by conventional endoscopic and barium contrast examinations.

Adult↗
PubMed1976

Triage for the breast biopsy.

A plan is advocated for the management of the dominant breast mass with use of local anesthesia in the outpatient setting as the primary diagnostic tool, but with selection of certain patients for immediate general anesthesia biopsy in the "conventional" manner. Experience with this plan in 2,492 patients during a period of 114 months shows local anesthesia biopsy to be efficient and accurate. Five year survival for all mastectomy-treated patients whose cancers were diagnosed under local anesthesia is 72 per cent. Use of a triage method for selecting biopsy procedures has resulted in a thirteen-fold decrease in the number of patients subjected to general anesthesia.

Adult↗