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Biomedical subjects

S C Jacobs

Publications and source records attributed to S C Jacobs.

At least 91 records · Page 5Linked to original sources
PubMed1993

Small bowel obstruction following laparoscopic lymphadenectomy.

We report 2 cases of small bowel obstruction following staging laparoscopic pelvic lymph node dissection for prostate adenocarcinoma. Short segments of ileum became incarcerated in the right lower abdominal trocar sites (10 mm.) in both patients. Laparotomy was done to repair the problem in both cases and in 1 small bowel resection was required because of strangulation. This complication can probably be prevented in the majority of cases by meticulous attention to trocar site closure at the termination of a laparoscopic procedure.

Aged↗
PubMed1993

Combined antitumor effect of suramin plus irradiation in human prostate cancer cells: the role of apoptosis.

Suramin has recently surfaced as a potential antineoplastic agent on the basis of its ability to exert a cytostatic effect on human prostate carcinoma cells. Radiotherapy for the treatment of prostate cancer has long been known as an alternative medical therapeutic approach, but the molecular mechanism involved in radiation-induced toxicity in prostatic tumors is poorly defined. In these studies, the antitumor effect of suramin and irradiation, either as individual treatments or in combination, was investigated in human prostate cancer cells. Two androgen-independent prostate cancer cell lines, DU-145 and PC-3, were used as in vitro model systems to study the underlying molecular mechanisms of these two therapeutic modalities. A cytostatic effect on cell growth was observed when cells were exposed to suramin alone, while treatment with irradiation alone resulted in significant cell death as determined by the Trypan blue exclusion assay. Suramin treatment prior to irradiation inhibited this radiation-induced cell death. In contrast, exposure of cells to suramin following irradiation enhanced the cytotoxic effect of ionizing radiation. Temporal analysis of the molecular events involved in radiation-induced toxicity revealed the characteristic fragmentation of DNA into a nucleosomal ladder (a hallmark of apoptosis) and enhanced expression of specific programmed cell death-associated genes (TRPM-2 and TGF-beta), preceding the dramatic decrease in cell number. These results indicate that radiation-induced cell death proceeds via the apoptotic pathway. Further studies have demonstrated that activation of programmed cell death by ionizing radiation is substantially inhibited by pretreatment of the cells with suramin. This study suggests that the relative timing of this combination treatment may have significant therapeutic implications in the treatment of advanced prostate cancer.

Apoptosis↗
PubMed1993

Late invasive recurrence despite long-term surveillance for superficial bladder cancer.

Superficial transitional cell carcinoma of the bladder is associated with a 15 to 70% recurrence rate within 2 years. Most recurrences are superficial. A recurrence after 2 disease-free years is unusual. A review of the tumor registry revealed 124 patients followed for superficial disease at the Veterans Administration Center in Baltimore. Of the patients 20 were identified with either stage Ta (7) or stage T1 (13) papillary transitional cell carcinoma who had completed at least 5 years of surveillance without tumor recurrence. Invasive transitional cell carcinoma of the bladder requiring cystectomy developed in 7 of these 20 patients after remaining tumor-free for 5 years (stage Ta in 4 and stage T1 in 3). All 7 patients had organ-confined disease and were alive with no evidence of disease at 18 months to 5 years after cystectomy. These results demonstrate that superficial, low grade transitional cell carcinoma of the bladder can become muscle invasive despite careful surveillance and a long dormant period. In our series yearly cystoscopy and urine cytology identified tumor recurrence before metastases developed, suggesting that long-term surveillance is required in patients with superficial bladder cancer.

Aged↗
PubMed1993

Hyperbaric oxygen treatment for experimental cyclophosphamide-induced hemorrhagic cystitis.

Acrolein is a toxic metabolite of cyclophosphamide that causes hemorrhagic cystitis in 2 to 40% of treated patients. Hyperbaric oxygen (HBO) is used to treat poorly healing wounds in conditions such as Fournier's gangrene and radiation-induced cystitis. The present study was designed to evaluate the effects of HBO on acute acrolein-induced hemorrhagic cystitis in a rat model. Rats were divided into 4 groups. Group I served as a control and received only HBO prior to sacrifice. Group II received acrolein only, while groups III and IV received acrolein as well as HBO therapy. Hyperbaric oxygen (100% oxygen, 2.8 atmospheres, 90 minutes) was delivered twice a day for 4 days, with group III receiving a fifth HBO treatment just before acrolein and group IV receiving the fifth HBO treatment just after acrolein. After therapy, the amount of urothelial injury was determined morphometrically. Group II untreated rat bladders had only 33% of the urothelium intact after acrolein injury, whereas groups III and IV rat bladders had 93% (p < 0.01) and 55% (p < 0.01) intact urothelium, respectively, after treatment with HBO. The timing of the HBO treatment appeared to be a critical factor, with less injury occurring if the fifth HBO treatment immediately preceded acrolein. These results suggest that HBO may be useful as prophylaxis and treatment of cyclophosphamide-induced hemorrhagic cystitis.

Acrolein↗
PubMed1993

Complications of staging laparoscopic pelvic lymphadenectomy.

Fifty-four patients underwent staging laparoscopic pelvic lymphadenectomy under general anesthesia for prostatic carcinoma (49), bladder carcinoma (3), penile carcinoma (1), and lymphoma (1). Conversion to an open procedure occurred only once in the series, but three patients received secondary open operations (5.5%). Complications recognized intraoperatively included bladder perforation (2) and mesenteric hematoma (1). One bladder perforation was repaired laparoscopically. The other was treated with catheter drainage. The mesenteric hematoma was explored surgically and found to be minor. Major postoperative complications included bleeding (4) requiring transfusion in two patients. One hematoma became infected requiring percutaneous drainage. One patient required intubation due to chronic obstructive pulmonary disease (COPD). Ureteral injury (1) was recognized late and required a psoas hitch and ureteroneocystostomy. Two patients developed small bowel obstructions due to herniation through a trocar site, requiring operative correction. Minor postoperative complications included ileus (4), diarrhea (2), bronchospasm (1), transient obturator nerve palsy (1), electrocardiogram changes (1), and fever (1). The overall major complication rate was 16.7%, and the overall minor complication rate was 18.4%. In this series, a substantial learning curve was seen with regard to complications, but the series compared favorably with open lymphadenectomy.

Adult↗
PubMed1993

Seizures associated with antidepressants: a review.

BACKGROUND: Seizures are uncommon, but serious, adverse effects of antidepressant drugs. A better understanding of drug-related seizure risk, its predictors, and its neurophysiologic basis might help clinicians avoid this adverse event. A better understanding of the factors involved in the determination of seizure risk would be helpful for interpretation of seizure rates reported. METHOD: The authors review case reports, series of cases, and information from clinical trials of antidepressants to determine antidepressant-related seizure risk. Predisposing factors are identified. Effects of dose, blood levels, and duration of treatment on seizure risk are examined. Electrophysiologic and in vitro models of drug-related seizure induction are discussed. RESULTS: A significant proportion of drug-related seizures occurs in individuals with an identifiable predisposition, such as previous seizures, sedative or alcohol withdrawal, and multiple concomitant medications. Seizure risk for most antidepressants increases with dose (or blood level), and comparisons between drugs should consider seizure rates at the effective dose (or blood level) for each drug. For imipramine, the most frequently studied tricyclic, the literature indicates a seizure rate between 0.3% and 0.6% at effective doses. In unselected patients and at higher doses, these rates may be higher. Fluoxetine, sertraline, fluvoxamine, trazodone, nomifensine, and the monoamine oxidase inhibitors have a lower seizure risk. Estimates for recently marketed antidepressants with intermediate seizure risk are complicated by the fact that effective doses and blood levels are not well established. CONCLUSION: Assessment of seizure risk in individuals involves consideration of predisposing factors, the antidepressant selected, and the bioavailability of the drug. Future studies of seizure risk would benefit from the use of specified criteria for determination of probable seizure events, a priori definition of predisposing exclusions, samples sufficiently large to provide adequate power, blood level monitoring, and inclusion of duration of drug treatment in the calculation of risk.

Antidepressive Agents↗
PubMed1992

Tocopherol analogs suppress arachidonic acid metabolism via phospholipase inhibition.

alpha-Tocopherol and three derivatives in which the phytol chain is modified or deleted were examined for their effect on cultured keratinocyte arachidonic acid metabolism. 2,2,5,7,8-Pentamethyl-6-hydroxychromane (PMC), in which the phytol chain is replaced by a methyl group, inhibited basal, bradykinin (BK)- and A23187-stimulated prostaglandin E2 (PGE2) synthesis with an apparent Ki of 1.3 microM. The Ki of the analogue with six carbon atoms in the side chain (C6) was 5 microM while that of the C11 analogue was 10 microM. No effect of alpha-tocopherol was observed. The mechanism of inhibition was studied using PMC. The effect of PMC on phospholipase and cyclooxygenase activity was assayed using stable isotope mass measurements of PGE2 formation, which assesses arachidonate release and cyclooxygenase metabolism simultaneously. BK-stimulated formation of PGE2, derived from endogenous phospholipid, was decreased 60% by 5 microM PMC and eliminated by 50 microM PMC, compared with controls. No difference in PGE2 formed from exogenous arachidonic acid was observed, indicating no effect of PMC on cyclooxygenase activity. In contrast, no effect of 5 microM PMC was observed on BK-stimulated [3H]arachidonic acid release from prelabeled cultures. The capacity of PMC to inhibit phospholipase activity in vitro was also assessed. PMC inhibited hydrolysis of phospholipid substrate by up to 60%. These results suggest that alpha-tocopherol analogues with alterations in the phytol chain inhibit eicosanoid synthesis by preferential inhibition of phospholipase.

Arachidonic Acids↗
PubMed1992

Enhanced neurovirulence of tick-borne orbiviruses resulting from genetic modulation.

The genome of orbiviruses (Reoviridae family) comprises 10 segments of double-stranded RNA. The fourth largest segment of the tick-borne Kemerovo (KEM) group orbiviruses is the genetic determinant of neurovirulence in experimentally infected mice, and segment 6 determines serotype. Reassortant viruses derived from a cross between two KEM-related viruses, Great Island (GI) and Wexford (WEX), that had the heterotypic gene combination W4G6 (segment 4 of WEX virus and segment 6 from GI virus) were nonpathogenic in mice. This apparent genetic modulation of neurovirulence may have resulted from steric interaction between the two outer capsid proteins of nonpathogenic reassortants. Further data are consistent with this hypothesis. Reassortants generated from additional KEM group viruses showed various degrees of enhanced neurovirulence in terms of their PFU/LD50 (ratio of infectivity in cell culture and in mice) and ASTmax (the average survival time at the highest virus dilution resulting in 100% mortality). Some reassortants were more pathogenic than either of their parental viruses. The results indicate that the gene determining neurovirulence dictates ASTmax, and the PFU/LD50 is a measure of the interaction between the products of the gene determining neurovirulence and that determining serotype. The nonpathogenic phenotype of a low passage isolate (St. Abb's 84-34 virus), derived from a single tick, generated neurovirulent reassortants. This result indicates that genetic modulation of KEM group viruses may occur in nature.

Animals↗
PubMed1992

Ureteral injury due to blunt and penetrating trauma.

In a period of twenty-seven months, 15 patients with ureteral trauma were encountered, leading us to believe that there is an increasing incidence of these injuries. The injuries were caused by blunt trauma in 3 patients and gunshot wounds in 12. All patients sustained injuries to other organs as well as the ureter. The diagnosis of ureteral injury was frequently delayed beyond the day of presentation (33%) primarily due to the number and severity of associated injuries. The most accurate methods of diagnosis were surgical exploration and retrograde pyelography. Intravenous pyelography and abdominal computerized tomography scanning were diagnostic in only 33 percent of cases. Hematuria was present in only 63 percent of patients who had no other genitourinary injuries, emphasizing the lack of reliability of this sign in ureteral trauma.

Adolescent↗
PubMed1992

Late development of renal carcinoma in allograft kidney.

The Cincinnati Transplant Tumor Registry recorded 169 cases of renal carcinoma developing in transplant recipients. The great majority of these cases were of primary renal cell carcinoma developing in the recipient native kidneys. Renal carcinoma developing de novo in the renal allograft occurred 17 times, with a maximal interval to clinical development of 85 months after transplantation. The development of multicentric renal cell carcinoma in an allograft 156 months after transplantation is described. The 24-year-old white male recipient with Alport's syndrome received a cadaver renal allograft from a healthy 27-year-old black man who had died of a cerebral hemorrhage in 1977. At 13 years after transplantation the recipient had upper abdominal pain. Ultrasound revealed 2 incidental renal masses and a renal cyst in the allograft. Partial nephrectomy confirmed the presence of multicentric renal carcinoma. The graft was left in situ and immunosuppression was maintained. The recipient continued to do well with no evidence of disease 1 year postoperatively. Deoxyribonucleic acid banding demonstrated that the tumor and recipient blood were of different patterns.

Adult↗
PubMed1992

Toxic shock syndrome: a complication of continent urinary diversion.

Toxic shock syndrome, a potentially lethal multisystem illness that usually affects menstruating women, is characterized by the acute onset of fever, hypotension, skin and mucous membrane changes, nausea, vomiting, diarrhea, myalgias, capillary leak, vascular collapse and multiorgan dysfunction. The disease is mediated by toxin produced by distinct strains of Staphylococcus aureus. We describe a case in which a toxin producing strain growing in a continent urinary diversion produced toxic shock syndrome.

Adolescent↗
PubMed1992

High-level expression of the tick-borne encephalitis virus NS1 protein by using an adenovirus-based vector: protection elicited in a murine model.

Tick-borne encephalitis virus (TBEV) encodes an abundant, highly immunogenic nonstructural glycoprotein, NS1. The function of this protein has yet to be determined. We have cloned the NS1 gene from the Neudorfl strain of TBEV under the control of the powerful constitutive cytomegalovirus major immediate-early promoter into an adenovirus E1 deletion mutant. The novel combination of the cytomegalovirus immediate-early promoter and the adenovirus vector produced extremely high levels of NS1 expression in cells which do not support replication of the adenovirus deletion mutant. The recombinant protein was shown to be indistinguishable from authentic TBEV NS1 in its (i) apparent molecular weight by polyacrylamide gel electrophoresis, (ii) glycosylation pattern, (iii) ability to form high-molecular-weight complexes, and (iv) ability to be secreted from cells. Appropriate processing of NS1 expressed by the adenovirus recombinant occurred independently of any additional TBEV-encoded gene function. When directly inoculated into mice, the recombinant adenovirus RAd51 was shown to elicit an antibody response to the TBEV NS1 protein. Immunization with RAd51 conferred protection against challenge with TBEV.

Adenoviridae↗
PubMed1991

Bradykinin-induced prostaglandin synthesis is enhanced in keratinocytes and fibroblasts by UV injury.

Ultraviolet (UV) light exposure substantially modifies the host immune response, in part through the synthesis of prostaglandins. Work examining the mechanisms by which UV irradiation stimulates prostaglandin synthesis has focused on mediators that increase in quantity after irradiation. The present work demonstrates that UV irradiation injury increases the sensitivity and maximum response of keratinocytes to bradykinin, suggesting that agonist quantities need not increase in injured tissue to contribute to inflammation. The ability of UV injury to increase bradykinin-stimulated prostaglandin synthesis is not limited to keratinocytes, as irradiation produced a similar response in fibroblasts. Receptor binding studies demonstrate that the enhanced response of irradiated cells is not due to increased bradykinin binding. These data suggest that UV irradiation may cause cells to increase their response to an array of inflammatory mediators present in injured tissue, whether or not the quantity of the mediator increases.

Bradykinin↗
PubMed1991

Laparoscopic pelvic lymphadenectomy.

Eleven male patients with pelvic malignancy underwent laparoscopic lymphadenectomy for staging of their tumors. The technique allowed removal of pelvic lymph nodes in all 11 patients and metastatic disease was found in five cases, resulting in a change of recommended therapy. The technique was via a three-port exposure, although a fourth suprapubic port was occasionally used for additional retraction. A bladder laceration, which was repaired laparoscopically, was the only intraoperative complication. A pelvic hematoma was the only significant postoperative complication. Laparoscopic pelvic lymphadenectomy appears to offer a less morbid staging for those patients with a high likelihood of nodal metastasis. Laparoscopic detection of positive pelvic lymph nodes may alter the management of genitourinary malignancy and improve overall patient care.

Acid Phosphatase↗