Biomedical subjects

R S Berman

Publications and source records attributed to R S Berman.

At least 19 recordsLinked to original sources

PubMed2001

A randomized double-blind study of caspofungin versus amphotericin for the treatment of candidal esophagitis.

Caspofungin is a new broad-spectrum antifungal drug. A multicenter, double-blind, randomized trial was conducted to assess the efficacy, safety, and tolerability of caspofungin relative to amphotericin B in adults with endoscopically documented symptomatic Candida esophagitis. By use of a modified intent-to-treat analysis, endoscopically verified clinical success was achieved in 74% (95% confidence interval [CI], 59%-86%) and 89% (95% CI, 72%-98%) of patients receiving caspofungin at 50 and 70 mg/day, respectively, and in 63% (95% CI, 49%-76%) of patients given amphotericin B at 0.5 mg/kg/day. Therapy was stopped because of drug-related adverse events in 24% of patients in the amphotericin B group and 4% and 7%, respectively, for the caspofungin groups. This report provides the first demonstration of clinical utility for an echinocandin compound. Caspofungin appeared in this study to be as effective as and better tolerated than amphotericin B for the treatment of esophageal candidiasis.

Adult↗

PubMed2001

Biology of liver metastases.

A primary goal of cancer research is an increased understanding of the molecular mechanisms mediating the process of cancer metastasis. Analyses of colon cancer cells (the seeds) and the microenvironment (the soil) have increased our understanding of the biologic mechanisms mediating metastasis formation. Insight into the molecular mechanisms regulating the pathobiology of colon cancer metastasis, as well as a better understanding of the interaction between the metastatic cell and the host environment (including the vasculature), should provide a foundation for new therapeutic approaches. To the clinician, it is readily apparent that by the time metastases form, most steps in the metastatic cascade have completed. Therefore, therapy to down-regulate or interrupt the last stages of metastasis, proliferation and angiogenesis as well as mechanisms to disrupt cell survival signals seems the most promising areas of investigation.

Genes, Tumor Suppressor↗

PubMed2000

Regional nodal basin control is not compromised by previous sentinel lymph node biopsy in patients with melanoma.

BACKGROUND: Regional nodal basin control is an important goal of lymphadenectomy in the management of melanoma patients with nodal disease. The purpose of this study was to determine if previous sentinel lymph node (SLN) biopsy compromises the ultimate regional nodal control achieved by subsequent therapeutic lymph node dissection in melanoma patients with microscopic lymph node metastases. METHODS: A surgical melanoma database and hospital records were reviewed for 602 patients with primary cutaneous melanoma who underwent successful lymphatic mapping and SLN biopsy between 1991 and 1997. RESULTS: A total of 105 (17%) of 602 patients had histologically positive SLNs and were offered therapeutic lymphadenectomy; 101 (96%) underwent this procedure. Thirty-six patients (36%) developed recurrent melanoma at one or more sites. The median follow-up period was 30 months. Recurrence in the previously dissected nodal basin was observed in 10 patients (10%); none had recurrence at only that site. Nodal basin disease appeared after local/in-transit (n = 6) or distant (n = 1) failure in seven patients and, as a component of the first site of failure, simultaneously with local/in-transit (n = 2) or distant (n = 1) recurrence in three patients. CONCLUSIONS: Nodal basin failure after lymphadenectomy in patients who underwent previous biopsy of a histologically positive SLN is primarily a function of aggressive locoregional disease rather than of contamination from previous surgery. Because regional nodal control was comparable with that in other series, we conclude that SLN biopsy with selective lymphadenectomy does not compromise regional nodal basin control.

Adolescent↗

PubMed2000

Significance of multiple nodal basin drainage in truncal melanoma patients undergoing sentinel lymph node biopsy.

BACKGROUND: Although previous studies have demonstrated that truncal site is associated with an adverse prognosis, explanations for such risk are lacking. In addition, the number of nodal basins as well as the number of lymph nodes containing regional metastases are important prognostic factors in these patients. Because the lymphatic drainage pattern of truncal melanoma often includes more than one basin, we designed a study to evaluate (1) whether patients with multiple nodal basin drainage (MNBD) were at an increased risk of lymph node metastases identified by sentinel lymph node (SLN) biopsy, and (2) whether the histological status of an individual basin reliably predicted the status of the other draining basins in patients with MNBD. METHODS: The records of 295 consecutive truncal melanoma patients who were managed primarily with intraoperative lymphatic mapping and SLN biopsy, between 1991 and 1997, were reviewed. All patients underwent preoperative lymphoscintigraphy, which established the number and location of draining nodal basins. Univariate and multivariate analyses of relevant clinicopathological factors were performed to assess which factors may predict the presence of a pathologically positive SLN. RESULTS: At least one SLN was identified in 281 patients. MNBD was present in 86 (31%) patients, and a pathologically positive SLN was found in 56 (20%) patients. By multivariate analysis, the presence of MNBD (relative risk = 1.9; P = .03), tumor thickness (P = .007), and tumor ulceration (relative risk = 2.4; P = .01) were significant independent risk factors for the presence of at least one pathologically positive SLN. SLN pathology in one basin did not predict the histology of other basins in 19 (22%) of 86 patients with MNBD. CONCLUSIONS: MNBD is independently associated with an increased risk of nodal metastases in truncal melanoma patients. Because the histological status of an individual basin did not reliably predict the status of the other draining basins in patients with MNBD, it is important to adequately identify and completely assess all nodal basins at risk, as defined by lymphoscintigraphy, in truncal melanoma patients.

Biopsy↗

PubMed2000

How many lymph nodes are enough during sentinel lymphadenectomy for primary melanoma?

BACKGROUND: Sentinel lymph node (SLN) biopsy has been shown to reliably identify nodal metastases and the subsequent need for further surgical and adjuvant therapy in patients with cutaneous melanoma. Although SLN identification rates have improved with the addition of radioactive colloid to the blue dye technique, it remains unclear how many lymph nodes should be removed to accurately determine the histologic status of the nodal basin. The objective of this study was to determine the optimal extent of SLN biopsy in these patients. METHODS: The records of 633 consecutive patients with melanoma (765 nodal basins) whose primary treatment included SLN biopsy with the use of a combination of blue dye and technetium Tc 99 labeled sulfur colloid were reviewed. SLN biopsy consisted of the removal of all of the blue-stained nodes and all nodes with radiotracer uptake activity of at least twice background. RESULTS: SLN biopsy was successful in 765 of 772 basins (99%). A mean of 1.9 SLNs (median, 2 SLNs) per basin were excised. At least 3 SLNs were removed in 176 basins (23%). The overall histologic status of a basin was always established by the first or second SLN harvested (ie, in no patient was the third or subsequent SLN positive when 1 of the first 2 was not). Of the 124 basins containing lymphatic metastases, the SLN that contained the maximal radiotracer uptake (hottest) and/or stained blue was pathologically positive in 118 basins (95%). In only 6 of the 124 positive basins (5%) was the sole evidence of occult nodal metastases identified in an SLN that was neither blue-stained nor the hottest. All but 1 of these SLNs had counts that were at least 66% of the hottest node in the basin. CONCLUSIONS: With a combined modality approach to SLN biopsy, removal of more than 2 SLNs did not provide information that upstaged any patient with primary melanoma. Removal of additional nonblue SLN(s) that contained radioactive counts of at least twice background but lower than two thirds of the SLNs with maximal radiotracer uptake affected patient management in less than 0.2% of all cases. These findings may be helpful in minimizing the extent of surgery and perhaps in reducing the costs and resource use associated with operating room time and pathologic examination.

Biopsy↗

PubMed1999

Laparoscopic splenectomy in patients with hematologic malignancies.

BACKGROUND: Although laparoscopic splenectomy (LS) for benign hematologic disease is well accepted, its role in hematologic malignancies is not clearly defined. This study examined the efficacy and feasibility of LS for hematologic malignancies. METHODS: Records were reviewed from patients who underwent LS at two university hospitals. Charts from 77 open splenectomies for malignancy (OM) during the same period were also reviewed. RESULTS: Fifty-three patients underwent LS, 22 for hematologic malignancies (LM) and 31 for benign hematologic disorders (LB). Median splenic weight was greater in the LM group (930 g) than in the LB group (164 g, P = 0.001). LM was associated with longer operations and greater blood loss than was LB. LM had a 41% conversion rate. Morbidity, mortality, and transfusion rates were similar. Median hospital stay was shorter for LM (4 days) than for OM (6 days, P = 0.001). CONCLUSIONS: LS is feasible in hematologic malignancies but is associated with increased operative time and blood loss and a high conversion rate. Morbidity and mortality, however, was similar. Shorter hospital stays for LM compared with OM may translate into earlier recovery and initiation of antineoplastic therapy.

Adult↗

PubMed1999

Growth hormone, alone and in combination with insulin, increases whole body and skeletal muscle protein kinetics in cancer patients after surgery.

OBJECTIVE: To investigate the impact of growth hormone, alone and in combination with insulin, on the protein kinetics of patients with upper gastrointestinal (GI) tract cancer who have undergone surgery and are receiving total parenteral nutrition (TPN). SUMMARY BACKGROUND DATA: Patients with malignancies of the upper GI tract are at increased risk for malnutrition and perioperative death and complications. Standard nutritional support has not significantly altered outcome. Growth hormone (GH) and insulin have been shown to have some benefit in patients with cancer; however, their action in patients undergoing resection has not previously been studied. METHODS: Thirty patients undergoing surgery for upper GI tract malignancies were prospectively randomized into one of three nutritional support groups after surgery: 10 patients received standard TPN, 10 received TPN plus daily injections of GH, and 10 received daily GH, systemic insulin, and TPN. The patients underwent a protein kinetic radiotracer study on the fifth day after surgery to determine whole body and skeletal muscle protein kinetics. RESULTS: Patients who received standard TPN only were in a state of negative skeletal muscle protein net balance. Those who received GH and insulin had improved skeletal muscle protein net balance compared with the TPN only group. Whole body protein net balance was improved in the GH and the GH and insulin groups compared with the TPN only group. GH and insulin combined did not improve whole body net balance more than GH alone. GH administration significantly increased serum IGF-1 and GH levels. Insulin infusion significantly increased serum insulin levels and the insulin/glucagon ratio. CONCLUSION: Growth hormone and GH plus insulin regimens improve protein kinetic parameters in patients with upper GI tract cancer who are receiving TPN after undergoing surgery.

Aged↗

PubMed1999

Long-term outcome of patients with American Joint Committee on Cancer stage IIB extremity soft tissue sarcomas.

PURPOSE: It has been suggested that patients with small (< 5 cm), high-grade extremity soft tissue sarcomas (STS) have an excellent overall prognosis and, consequently, may not require adjuvant therapies. PATIENTS AND METHODS: A comprehensive review of all patients with extremity STS treated at a tertiary care cancer hospital over a 9-year period (January 1984 to December 1992) was performed. Prognostic factors, treatment data, and long-term outcome were evaluated in the subset of 111 patients with American Joint Committee on Cancer stage IIB (G3/4, T1a/b) disease. RESULTS: The median tumor size was 3.0 cm (range, 0.6 to 4.9 cm), and 55 tumors (50%) were deep in location. All patients underwent surgical resection; 68 (61%) received pre- or postoperative radiotherapy, and 32 (29%) received doxorubicin-based chemotherapy. The median follow-up was 76 months. Forty patients (36%) experienced 59 recurrences. First recurrences occurred at local, regional, and distant sites in 21, five, and 14 patients, respectively. The 5-year actuarial local recurrence-free, distant recurrence-free, disease-free, and overall survival rates were 82%, 83%, 68%, and 83%, respectively. The presence of a microscopically positive surgical margin was an independent adverse prognostic factor for both local recurrence (relative risk [RR] = 3.75; 95% confidence interval [CI], 1.25 to 11.25; P =.02) and disease-free survival (RR = 2.57; 95% CI, 1.33 to 4.98; P =.005). CONCLUSION: Event-free outcome for this subset of patients with high-grade STS does not seem as favorable as previously reported by other investigators. Patients who undergo maximal surgical resection with microscopically positive margins represent a subset of T1 STS patients who warrant consideration for adjuvant therapies.

Adolescent↗

PubMed1998

Spatial heterogeneity in the mechanisms contributing to acetylcholine-induced dilatation in the rabbit isolated ear.

1. Using an X-ray microangiographic technique in rabbit isolated perfused ears preconstricted with 5-HT (300 nM) and histamine (300 nM), we investigated the combined actions of N(omega)-nitro-L-arginine methyl ester (L-NAME) and indomethacin on acetylcholine-induced depressor responses. 2. Under control conditions, acetylcholine (10 nM-30 microM) induced a concentration-dependent reversal of the pressor response, reaching a maximum of 66.0+/-13.6% (n = 6). In the presence of L-NAME (300 microM) and indomethacin (10 microM), this depressor action was reduced, reaching a maximum of 38.6+/-5.9% (n = 6). 3. The control response was associated with substantial vasodilatation in the central ear artery (G0), a smaller dilatory action on first generation branch arteries (G1) and no effect on second generation branch arteries (G2). In the presence of L-NAME and indomethacin, vasodilatation occurred in G2 with no effect in G0 or G1. 4. Two calcium-activated K+ channels blockers, charybdotoxin (ChTX; 10 nM) and penitrem A (100 nM), further inhibited, but did not abolish, the L-NAME- and indomethacin-resistant response to acetylcholine (10 nM-300 microM). Both agents abolished the vasodilatory action of acetylcholine in G2. 5. In conclusion, L-NAME and indomethacin induced a shift in acetylcholine-induced vasodilatation from G0 and G1 to G2. This is consistent with the suggestion that nitric oxide dominates in larger vessels whilst other mechanisms dominate in smaller vessels. The L-NAME- and indomethacin-resistant component was inhibited by ChTX and penitrem A, suggesting it is mediated, at least in part, by activation of K(Ca) channels and could therefore involve a hyperpolarising mediator such as endothelium-derived hyperpolarising factor.

Acetylcholine↗

PubMed1997

Differential actions of charybdotoxin on central and daughter branch arteries of the rabbit isolated ear.

1. By use of rabbit isolated perfused intact ears and isolated perfused segments of central and first generation daughter branch ear arteries, we investigated the actions of charybdotoxin (ChTX), a blocker of calcium-activated K+ channels (KCa channels), and N omega-nitro-L-arginine methyl ester (L-NAME) on pressure-flow and diameter-flow relationships. 2. ChTX (1 nM) induced an upwards shift in the pressure-flow curve in the rabbit intact isolated ear preconstricted with 5-hydroxytryptamine (5-HT; 100 nM) with subsequent administration of L-NAME (100 microM) inducing a further upwards shift. L-NAME itself induced an upwards shift in the pressure-flow curve, but subsequent administration of ChTX was without significant effect. 3. Microangiographic analysis revealed a tendency of ChTX (1 nM) to decrease vessel diameter in the central ear artery (G0) with little effect on the first two generations of daughter branch arteries (G1 and G2) in the intact ear. Subsequent addition of L-NAME (100 microM) did not significantly further decrease vessel diameter in G0, but did decrease vessel diameter in G1 and G2. L-NAME itself showed a tendency to decrease vessel diameter in G0, G1 and G2 vessels with subsequent addition of ChTX being without significant effect. 4. In an isolated G0 preparation which was preconstricted with 5-HT (100 nM), ChTX (1 nM) caused an upwards shift in the pressure-flow curve which was augmented by subsequent addition of L-NAME (100 microM). L-NAME (100 microM) itself caused an upwards shift in the pressure-flow curve but subsequent addition of ChTX (1 nM) had no significant effect. 5. In comparison, in an isolated G1 preparation which was preconstricted with 5-HT (100 nM), ChTX (1 nM) had no significant effect on the pressure-flow curve relative to control, but subsequent addition of L-NAME (100 microM) caused an upwards shift. L-NAME (100 microM) itself induced an upwards shift in the pressure-flow curve with subsequent addition of ChTX (1 nM) being without significant effect. 6. ChTX (10 pM-10 nM) caused a concentration-dependent increase in perfusion pressure in isolated G0 and G1 preparations at fixed flow rates of 2 ml min-1 and 0.5 ml min-1, respectively. These responses were enhanced in the presence of L-NAME (100 microM) in G1 but not G0 preparations. 7. We conclude that at 1 nM, ChTX exhibits differential actions on central and daughter branch arteries of the intact ear of the rabbit, which are also apparent in the corresponding arteries when studied in isolation. The action of 1 nM ChTX in G0 vessels may reflect inhibition of either the release or action of nitric oxide as it was blocked in the presence of L-NAME. At higher concentrations of ChTX, there would appear to be a direct constrictor effect on vascular smooth muscle which is apparent in both G0 and G1 vessels. This observed heterogeneity could reflect different distributions of KCa channels between central and daughter branch arteries at either the endothelial or smooth muscle levels, or both.

Animals↗

PubMed1997

Risk factors associated with women's compliance with estrogen replacement therapy.

An epidemiologic study was carried out in 2106 women 46-63 years of age to determine risk factors associated with their compliance or noncompliance with estrogen replacement therapy (ERT). Data were obtained from prescription refill and medical claims information from centralized prescription and medical claims databases of a United Healthcare-affiliated health plan in Minnesota. Study participants filled their first ERT prescription during calendar year 1989 or 1990. Our results indicate that women who are older, use a progestin, experience hormone replacement therapy side effects, or see a gynecologist or male physician are more likely to be noncompliant. Women who have cardiovascular problems, experience menopausal symptoms, or use transdermal estrogen are more likely to be compliant. These results suggest that the factors associated with compliance are those that indicate that women perceive a benefit from ERT use. The factors associated with noncompliance are hormone side effects and gender and specialty of the physician prescribing the estrogen.

Aged↗

PubMed1994

Effect of systemic insulin on protein kinetics in postoperative cancer patients.

BACKGROUND: Cancer cachexia is a significant cause of postoperative morbidity and mortality in patients with tumors of the upper gastrointestinal tract. Standard parenteral nutrition (TPN) has failed to alter this. The anabolic effect of insulin has been well documented, and its positive effect on protein economy in cancer patients has been recently demonstrated. This study examines the effect of high-dose insulin and parenteral nutrition on protein kinetics in postoperative cancer patients. METHODS: Eleven patients underwent surgery for pancreatic, esophageal, or gastric carcinoma. Postoperatively, patients received standard TPN for 4 days (1 g/kg/day amino acids, 1,000 kcal/day dextrose, 100 g/day lipid), and hyperinsulinemic parenteral nutrition for 4 days (same as standard TPN plus 1.44 U/kg/day regular human insulin) in a crossover design. All patients received both treatments, and the order of treatment was determined randomly. Euglycemia was maintained during insulin infusion via a variable 30% dextrose infusion. Patients underwent protein metabolic studies after each treatment period and rates of whole body and skeletal muscle protein synthesis, breakdown, and net balance were determined by radioisotopic tracer methods using 14C-leucine and 3H-phenylalanine. RESULTS: Compared with standard TPN (STD), hyperinsulinemic TPN (INS) resulted in a significant increase in skeletal muscle protein synthesis (INS: 52.04 +/- 10.22 versus STD: 26.06 +/- 6.71 nmol phe/100 g/min, p < 0.05) and net balance of protein (INS: 7.75 +/- 4.61 versus STD: -15.10 +/- 6.44 nmol phe/100 g/min, p < 0.01), but no difference in skeletal muscle protein breakdown (INS: 44.29 +/- 11.54 versus STD: 41.17 +/- 5.89 nmol phe/100 g/min). Whole-body net balance of protein also significantly increased with insulin-based TPN, compared with standard TPN (INS: 0.04 +/- 0.05 versus STD: -0.08 +/- 0.07 mumol leu/kg/min, p < 0.05), but no difference in whole-body protein synthesis (INS: 2.52 +/- 0.15 versus STD: 2.49 +/- 0.15 mumol leu/kg/min) or whole-body protein breakdown (INS: 2.48 +/- 0.16 versus STD: 2.58 +/- 0.19 mumol leu/kg/min) was observed. Patients received significantly more calories during the hyperinsulinemic TPN period than during the standard TPN period. There was no difference in total, essential, or branched-chain amino acids, and no difference in serum free fatty acids, triglycerides, or cholesterol was observed between the two treatment periods. CONCLUSION: High-dose insulin in conjunction with hypercaloric parenteral nutrition causes improved skeletal muscle protein synthesis, skeletal muscle protein net balance, and whole-body protein net balance compared with standard TPN in postoperative cancer patients.

Adult↗

PubMed1994

Pharmacodynamic activity of intravenous E-3174, an angiotensin II antagonist, in patients with essential hypertension.

Losartan potassium (DuP 753), an orally active angiotensin II receptor antagonist, is metabolized to a more potent active metabolite, E-3174, which contributes to losartan's long duration of action. The acute pharmacodynamic actions of intravenous (i.v.) E-3174 (20 mg infused over 4 h) were compared to placebo (vehicle) in two groups of patients with essential hypertension. Patients with supine diastolic blood pressure (SuDBP) of 100 to 120 mm Hg entered a 2-day inpatient phase and received vehicle on day 1. Patients with SuDBP > or = 95 mm Hg were randomized to double-blind treatment the next day. E-3174 significantly (P < .05) reduced SuDBP compared to placebo, beginning at approximately 100 min after the start of the infusion, with a maximum hypotensive effect at 8 h. Supine systolic blood pressure was also reduced by E-3174. Supine and standing heart rates did not differ between treatments. Mean E-3174 plasma levels were 324.6 ng/mL at 20 min and approximately 1000 ng/mL at the end of the 4-h infusion; during this time there was a modest decrease in blood pressure. Following the infusion, the relationship between plasma E-3174 levels and SuDBP was confounded by much larger decreases in blood pressure, which occurred as plasma drug concentrations declined. Urinary excretions of sodium, potassium, or chloride were not significantly altered by E-3174 nor was the fractional excretion of uric acid significantly different between groups. There were no drug-related or serious adverse experiences and no patient discontinued treatment due to an adverse experience.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Arterial endothelial barrier dysfunction: actions of homocysteine and the hypoxanthine-xanthine oxidase free radical generating system.

1. Endothelial barrier function was assessed by use of an in vitro model in which transfer of trypan blue-labelled albumin was measured across monolayers of bovine aortic endothelial cells grown on polycarbonate membranes. 2. Addition of either hypoxanthine (0.2 mM) or xanthine oxidase (20 mu ml-1) alone during a 90 min incubation did not affect albumin transfer across endothelial cell monolayers, but a combination of both increased transfer. 3. The increase in albumin transfer induced by hypoxanthine and xanthine oxidase was abolished by catalase (3 u ml-1), reduced by allopurinol (4 mM), but unaffected by superoxide dismutase (6000 u ml-1), the hydroxyl radical scavengers, mannitol (15 mM), dimethylthiourea (10 mM) and N-(2-mercaptopropionyl)-glycine (1 mM), the iron chelator, deferoxamine (0.5 mM), ferric chloride (50 microM), an inhibitor of nitric oxide synthase, NG-nitro-L-arginine (30 microM), or the antioxidant, dithiothreitol (3 mM). 4. Hydrogen peroxide (0.1-30 mM) itself increased albumin transfer across endothelial cell monolayers, exhibiting a biphasic concentration-response curve. The increase induced by 0.1 mM hydrogen peroxide was abolished in the presence of 0.3 u ml-1 catalase whilst that induced by 10 mM hydrogen peroxide was abolished by 3000 u ml-1 catalase. 5. Homocysteine (0.5-1.5 mM) did not affect albumin transfer across endothelial monolayers when added alone, but when added in combination with copper sulphate (50 microM), which catalyses its oxidation, a significant increase in albumin transfer was observed. 6. The increase in albumin transfer induced by the combination of homocysteine (1.5 mM) and copper sulphate was abolished by catalase (1 u ml-1), but was unaffected by superoxide dismutase (6000 u ml-1), mannitol (15 mM), dimethylthiourea (1 mM) or deferoxamine (0.5 mM).7. The data suggest that the endothelial barrier dysfunction induced by the combination of hypoxanthine and xanthine oxidase is mediated solely by the action of hydrogen peroxide and not by superoxide anion, hydroxyl radical, peroxynitrite anion or hypochlorous acid. The copper-catalysed oxidation of homocysteine also induces endothelial barrier dysfunction through the generation of hydrogen peroxide.These findings may have relevance to the endothelial barrier dysfunction associated with ischaemia reperfusion injury and the atherogenic actions of homocysteine.

Albumins↗

PubMed1993

Endotoxin-induced arterial endothelial barrier dysfunction assessed by an in vitro model.

Using an in vitro model in which albumin transfer across monolayers of bovine aortic endothelial cells (BAEC) was measured, we have shown that lipopolysaccharide (LPS) induces a concentration-dependent increase in endothelial permeability. This increase was biphasic, having an early peak at 2 h and rising again by 24 h. Both peaks were abolished by polymixin B (PMB) but were unaffected by N omega-monomethyl-L-arginine, N omega-nitro-L-arginine methyl ester or dexamethasone. Furthermore, LPS did not stimulate nitric oxide production by BAEC following 24 h exposure. Thus, the LPS-induced increase in permeability may account for the vascular leakage of septic shock, but the L-arginine-nitric oxide system does not appear to be involved.

Albumins↗

PubMed1990

Bone marrow transplantation (BMT) for the syndrome of pigmentary dilution and lymphohistiocytosis (Griscelli's syndrome).

We report the successful treatment of the syndrome of pigmentary dilution and immunodeficiency (Griscelli's syndrome) with allogeneic bone marrow transplantation. Griscelli's syndrome includes silvery hair, recurrent infections, hepatosplenomegaly, progressive neurologic deterioration, and lymphohistiocytosis and is uniformly fatal. We present a family in which four of seven children of consanguinous parents were affected. The affected children were all born with silvery hair. Microscopic examination of the hair showed large clumps of pigment in the hair shaft. Skin biopsy revealed an accumulation of melanosomes in the melanocytes. Three of the affected children were deceased before 20 months of age. Pathology of liver and lung in two of the siblings showed an infiltration of lymphocytes and histiocytes. Immunologic studies in one of these cases were notable for a decreased number of T cells and poor T-cell mitogen stimulation with concanavalin A (Con A) and pokeweed mitogen (PWM). Recently, a fourth sibling with silvery gray hair was referred to us at 3 months of age for evaluation. T-cell function studies were normal and she appeared in overall good health. Because of the expected fatal outcome, allogeneic bone marrow transplantation was performed at 4 months of age. Two years later the patient remains in excellent health. This suggests that cells of hematopoietic origin are responsible for the fatal outcome in Griscelli's syndrome and that bone marrow transplantation early in the course of the disease is an important modality for treatment of this syndrome.

Bone Marrow Transplantation↗

PubMed1990

Omeprazole versus placebo in duodenal ulcer healing. The United States experience.

The study objective was to study the ulcer healing effects and safety of the proton pump inhibitor, omeprazole, given in a dose of 20 mg once daily before breakfast. The study design was a randomized, double-blind, multicenter comparison of omeprazole and placebo using endoscopy to assess ulcer healing after two or four weeks of therapy. One hundred fifty-three patients with endoscopically documented active duodenal ulcer were studied. One hundred two patients received omeprazole and 51 received placebo. Patients in both groups were similar with regard to age, sex, duration of disease, initial ulcer size, smoking history, and alcohol use. A "per protocol" analysis of healing rates showed a significant advantage for omeprazole (P less than 0.01) at both week 2 (41% vs 13%) and week 4 (75% vs 27%). Concomitant factors (including smoking and ulcer size) did not alter the significance of the differences in healing rates between omeprazole and placebo. Complete relief of day and night pain was more often achieved (P less than 0.01) in the omeprazole group. "All-patients treated" analyses for healing and pain relief gave results similar to the respective "per protocol" analyses. Omeprazole was well tolerated; fewer patients had clinical and laboratory adverse experiences in the omeprazole group than in the placebo group. Fasting serum gastrin levels increased with omeprazole therapy (mean 34.9 to 73.5 pg/ml) but exceeded the normal range (greater than 150 pg/ml) in only 12.3% of patients. Two weeks after therapy was stopped, serum gastrin levels showed a decrease toward baseline but had not yet completely returned to pretreatment levels (mean 49.7 pg/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Double-Blind Method↗

PubMed1990

Long peritoneal lavage decreases pancreatic sepsis in acute pancreatitis.

Late infection of devitalized pancreatic and peripancreatic tissue has become the major cause of morbidity in severe acute pancreatitis. Previous experience found that peritoneal lavage for periods of 48 to 96 hours may reduce early systemic complications but did not decrease late pancreatic sepsis. A fortunate observation led to the present study of the influence of a longer period of lavage on late sepsis. Twenty-nine patients receiving primary nonoperative treatment for severe acute pancreatitis (three or more positive prognostic signs) were randomly assigned to short peritoneal lavage (SPL) for 2 days (15 patients) or to long peritoneal lavage (LPL) for 7 days (14 patients). Positive prognostic signs averaged 5 in both groups but the frequency of five or more signs was higher in LPL (71%) than in SPL (47%). Eleven patients in each group had early computed tomographic (CT) scans. Peripancreatic fluid collections were shown more commonly in LPL (82%) than in SPL (54%) patients. Longer lavage dramatically reduced the frequency of both pancreatic sepsis (22% LPL versus 40% SPL) and death from sepsis (0% LPL versus 20% SPL). Among patients with fluid collections on early CT scan, LPL led to a more marked reduction in both pancreatic sepsis (33% LPL versus 83% SPL) and death from sepsis (0% LPL versus 33% SPL). The differences were even more striking among 17 patients with five or more positive prognostic signs. In this group the incidence of pancreatic sepsis was 30% LPL versus 57% SPL and of death from sepsis 0% (LPL) versus 43% (SPL) (p = 0.05). In these patients, overall mortality was also reduced (20% LPL versus 43% SPL). When 20 patients treated by LPL were compared with 91 other patients with three or more positive prognostic signs who were treated without lavage or by lavage for periods of 2 to 4 days, the frequency of death from pancreatic sepsis was reduced from 13% to 5%. In those with five or more signs, the incidence of sepsis was reduced from 40% to 27% (p = 0.03) and of death for sepsis from 30% to 7% (p = 0.08). These findings indicate that lavage of the peritoneal cavity for 7 days may significantly reduce both the frequency and mortality rate of pancreatic sepsis in severe acute pancreatitis.

Abscess↗