PubMed Health⌕ Search

Biomedical subjects

W Benson

Publications and source records attributed to W Benson.

At least 19 recordsLinked to original sources
PubMed2003

Outpatient-based ifosfamide, carboplatin and etoposide (ICE) chemotherapy in transplant-eligible patients with non-Hodgkin's lymphoma and Hodgkin's disease.

We have treated 38 transplant-eligible patients with relapsed/refractory non-Hodgkin's lymphoma and Hodgkin's disease using an outpatient-based regimen of ifosfamide, carboplatin and etoposide (ICE) for both salvage and peripheral blood stem cell mobilisation. Patients included relapsed or refractory diffuse large B-cell lymphoma (n = 17), follicular lymphoma (n = II), T-cell lymphoma (n = 2), mantle cell lymphoma (n = 2) and Hodgkin's disease (n = 6). Seven patients with diffuse large B-cell lymphoma and three patients with follicular lymphoma (26%) were considered chemorefractory. Cycles of ICE therapy were administered every 21 days as an outpatient and consisted of ifosfamide 5000 mg/m2 intravenously (i.v.) fractionated into three equally divided doses over 3 days, carboplatin [mg dose = 5 x area under the curve (AUC)] i.v. on day 1 and etoposide 100 mg/m2- i.v. daily for 3 days. Subsequently. granulocyte colony-stimulating factor (G-CSF)5 microg/kg subcutaneously (s.c.) was administered daily from day +5. Of the I I follicular lymphoma patients, 10 also received rituximab with ICE therapy. Median age of patients was 52 years (range 30-65). Patients received a mean of 2.6 cycles (range 1-4) of ICE. There were no toxic deaths and no significant non-haematological toxicities secondary to ICE therapy. Grade IV thrombocytopenia and grade IV neutropenia with at least one cycle of ICE were seen in 47% and 53% of patients, respectively. Median time to peripheral blood stem cell (PBSC) harvest was 14 days (range 10-20). while the median CD34+ cell yield was 5.2 x 10(6) cells/kg(range 2.3 x 10(6)-27.2 x 10(6)). Only one of the ICE-responders failed to mobilise PBSCs. The overall response rate to ICE was 87%. comprising 14 patients (37%) who achieved a complete response (CR) and 19 (50%) who achieved a partial response (PR). A total of 30 patients have undergone autologous stem cell transplantation(SCT) while two follicular lymphoma patients have received a non-myeloablative allogeneic SCT. Follow-up is short: however, the Kaplan-Meier estimate of the proportion of patients alive and event-free at a median follow-up of 11 months is 80% and 59%, respectively. Event-free survival for patients who achieved a CR after ICE and transplantation is 88% versus 45% for those who achieved a PR. These data confirm the efficacy and tolerability of fractionated ICE chemotherapy as both a salvage and mobilisation regimen that can be readily delivered in an outpatient setting.

Adult↗
PubMed1999

Repeat exposure to incremental doses of acetaminophen provides protection against acetaminophen-induced lethality in mice: an explanation for high acetaminophen dosage in humans without hepatic injury.

In studies designed to simulate a clinical observation in which an individual became tolerant to normally lethal doses of acetaminophen (APAP), mice were pretreated with increasing doses of APAP for 8 days and challenged on day 9 with normally supralethal doses of APAP. These animals developed minimal hepatotoxicity after a challenge dose with a fourfold increase in LD50 to 1,350 mg/kg. The pretreatment regimen resulted in hepatic changes including: centrilobular localization of 3-(cysteine-S-yl)APAP protein adducts, selective down-regulation of cytochrome P4502E1 (CYP2E1) and CYP1A2 that produced the toxic metabolite, N-acetyl-p-benzoquinone imine, higher levels of reduced glutathione (GSH), centrilobular inflammation, and a fourfold increase in hepatocellular proliferation. The protection against the lethal APAP doses afforded by pretreatment is secondary to these changes and to the associated regional shift in the bioactivation of the APAP challenge dose from centrilobular to periportal regions where CYP2E1 is not found, protective GSH is more abundant, and where cell-proliferative responses are better able to sustain repair. This shift in APAP bioactivation results in less-intense covalent binding that is more diffuse and spread uniformly throughout the hepatic lobe, most likely contributing to protection by delaying the early onset of liver injury that has been generally associated with centrilobular localization of the adducts. Intervention of APAP pretreatment-induced cell division in mice with colchicine left them resistant to a 500-mg/kg (normally lethal) dose of APAP, but unable to survive a 1,000-mg/kg APAP challenge dose. The data demonstrate multiple mechanistic components to the protection afforded by APAP pretreatment. Whereas metabolic and physiological changes not dependent on cell proliferation are adequate to protect against 500 mg/kg APAP, these changes plus a potentiated cell-proliferative response are necessary for protection against the supralethal 1,000-mg/kg APAP dose. Furthermore, the data document an uncoupling of the traditional association between covalent binding and toxicity, and suggest that the assessment of toxicity following repeated or chronic APAP exposure must consider altered drug interactions and parameters besides those historically used to assess acute APAP overdose.

Acetaminophen↗
PubMed1998

Effects of keratinocyte growth factor on the proliferation and radiation survival of human squamous cell carcinoma cell lines in vitro and in vivo.

PURPOSE: Keratinocyte growth factor (KGF) has potent mitogenic activity on normal epithelial cells and has been found to enhance intestinal crypt cell survival in irradiated mice and to prevent radiation and chemotherapy-induced mucositis in animal models. The purpose of the study reported here is to investigate the effect of recombinant human KGF on the proliferation and survival of human squamous carcinoma cell lines following irradiation. METHODS AND MATERIALS: The level of KGF receptor (KGFR) mRNA in normal Balb/Mk cell line and human head and neck squamous carcinoma cell lines was assessed using a RNase protection assay. The clonogenic assay and MTT assay were used to study the proliferative effects of KGF on human tumor cell lines and Balb/MK cell line in vitro. Effects of KGF on in vivo tumor growth and radiosensitivity were studied in three KGFR-positive human squamous cell carcinoma xenografts (FaDu, Detroit 562 and A431) in nude mice, and a murine KGFR-negative melanoma tumor (B16) in Balb/c mice. RESULTS: Seven of 10 tumor cell lines studied expressed KGFR mRNA. None of these tumor cell lines showed enhanced proliferation when exposed to KGF for 2 days or less. Prolonged exposure to KGF for 7 days or longer resulted in low level stimulation of proliferation in both clonogenic and MTT assays in four of seven KGFR-positive cell lines. Two KGFR-negative cell lines also had a low proliferative response to KGF in a clonogenic assay, but not in the MTT assay. Normal keratinocyte Balb/MK cells, which expressed a moderate level of KGFR mRNA, had a strongly proliferative response to KGF. Its KGF enhancement ratio (KER) of plating efficiency was 24-70 times higher than that of the tumor cells studied (p < 0.001). The KGF-stimulated tumor cell growth was almost completely inhibited by heparin or epidermal growth factor (EGF). There were no significant differences (p > 0.05) in the survival of any of tumor cell lines in the presence or absence of KGF (100 ng/ml) irradiated with doses of 0-15 Gy, and no significant differences (p > 0.05) between the radiobiological parameters D0, Dq, and n number from the SHMT model, alpha, beta, and alpha/beta ratio from the LQ model and SF2 for radiation survival curves for cell lines irradiated in the presence or absence of KGF. Three KGFR-positive human squamous cell carcinoma xenografts in nude mice, and a murine KGFR-negative melanoma tumor in Balb/c mice treated with 1.0 mg/kg of KGF for 3 days grew at the same rate as in untreated mice. CONCLUSION: The recombinant human KGF resulted in little or no stimulation of the proliferation of human head and neck squamous tumor cell lines and did not affect the radiosensitivity of these cell lines in vitro and in vivo. Therefore, KGF may be of clinical value in preventing radiation-induced mucositis and may have the potential to increase the therapeutic index of radiotherapy for treatment of cancers.

Animals↗
PubMed1995

Keratinocyte growth factor is an important endogenous mediator of hair follicle growth, development, and differentiation. Normalization of the nu/nu follicular differentiation defect and amelioration of chemotherapy-induced alopecia.

The growth and development of hair follicles is influenced by a number of different growth factors and cytokines, particularly members of the fibroblast growth factor (FGF) family. Keratinocyte growth factor (KGF or FGF-7) is a recently identified 28-kd member of the FGF family that induces proliferation of a wide variety of epithelial cells, including keratinocytes within the epidermis and dermal adnexa. Because KGF induces marked proliferation of keratinocytes, and both KGF and KGF receptor (KGFR) mRNA are expressed at high levels in skin, we sought to localize KGF and KGFR in skin by in situ hybridization. KGFR mRNA was relatively strongly expressed by keratinocytes in the basilar epidermis as well as throughout developing hair follicles of rat embryos and neonates. KGF mRNA was expressed at lower levels than was KGFR but could be localized to follicular dermal papillae in rat embryos and neonates. These results prompted us to investigate the effects of KGF on hair follicles in two distinct murine models of alopecia. In the first model, recombinant KGF (rKGF) induced dose-dependent hair growth over most of the body in nu/nu athymic nude mice when administered intraperitoneally or subcutaneously over 17 to 18 days. When administered subcutaneously, rKGF induced the most extensive hair growth at the sites of injection. Histologically, rKGF induced marked follicular and sebaceous gland hypertrophy, a normalization of the nu/nu follicular keratinization defect, and an increase in follicular keratinocyte proliferation as assessed by bromodeoxyuridine labeling. In the second model, a neonatal rat model of cytosine arabinoside chemotherapy-induced alopecia in which interleukin-1, epidermal growth factor, and acidic FGF have all demonstrated some degree of alopecia cytoprotection, rKGF induced a dose-dependent cytoprotective effect, abrogating as much as 50% of the alopecia in this model when administered beginning 1 day before the onset of chemotherapy. Taken together, these data suggest that KGF is an important endogenous mediator of normal hair follicle growth, development, and differentiation.

Alopecia↗
PubMed1995

Keratinocyte growth factor causes proliferation of urothelium in vivo.

PURPOSE: To determine the effect of keratinocyte growth factor (KGF), a mesenchymally derived epithelial growth factor that can cause proliferation of pulmonary, gastrointestinal and mammary epithelia, on urothelium. MATERIALS AND METHODS: Recombinant human KGF was systemically administered to rats and Rhesus monkeys, and the proliferative effects on the bladder were evaluated. RESULTS: Keratinocyte growth factor causes proliferation of transitional epithelial cells. Proliferating cell nuclear antigen (PCNA) expression in rat bladder is dramatically increased along the basal layer of urothelium 1, 3, 7 and 14 days after daily injections of KGF. Incorporation of 5-bromodeoxyuridine (BrdU) at 7 and 14 days in the urothelium of KGF-treated rats parallels PCNA immunoreactivity and confirms that KGF increases DNA synthesis in urothelial cells. Urothelial cell proliferation is accompanied histologically by an increase in mitotic activity. Keratinocyte growth factor-induced PCNA expression is reversible upon cessation of KGF administration. Keratinocyte growth factor mRNA and receptor mRNA are detected by whole organ RNAase protection assays of the urinary bladder and the kidney of normal rats. Rhesus monkeys receiving KGF for 7 days demonstrate a dramatic incorporation of BrdU in the urothelium of the bladder and renal pelvis as well as in the collecting ducts of the kidney. CONCLUSION: Systemic administration of KGF causes rapid and striking proliferation of urothelium.

Animals↗
PubMed1995

Localization of human immunodeficiency virus 1 RNA in thymic tissues from asymptomatic drug addicts.

Thymic tissue was collected from 11 human immunodeficiency virus 1 (HIV-1)-seropositive drug users who died suddenly of drug intoxication or trauma. None of the 11 individuals had symptoms related to HIV-1 infection or were known to be seropositive for HIV-1 before death. Secondary B-cell follicles were present in every thymus, and Warthin-Finckeldey giant cells were noted in three cases. These follicles were enlarged or fragmented and appeared similar to those in lymph nodes excised from the same individuals. Localization of viral RNA by in situ hybridization demonstrated abundant virus in a follicular center cell distribution within hyperplastic follicles and in scattered medullary lymphocytes. In nine thymus glands from seronegative drug addicts and five thymus glands from seronegative trauma victims who were not drug addicts, secondary follicles were absent and no hybridization signal was present. Other than the presence of germinal centers associated with HIV-1 RNA, there were no histologic differences among the thymus glands of seropositive drug addicts, seronegative drug addicts, and seronegative controls without a history of drug abuse. We conclude that the thymus gland in early stages of infection with HIV-1 is characterized by induction of secondary B-cell follicular hyperplasia in medullary tissues, the germinal centers of which contain abundant viral RNA.

Adult↗
PubMed1993

The use of perfluorophenanthrene in the removal of intravitreal lens fragments.

We used perfluorophenanthrene as an aid during pars plana vitrectomy in removing lens fragments dislocated posteriorly into the vitreous cavity. We reviewed the records of all patients (nine patients, nine eyes) referred with dislocated lenses who underwent pars plana vitrectomy with perfluorophenanthrene for removal of the lens material at Wills Eye Hospital from July 1, 1991, through Nov. 30, 1991. The lens was dislocated during cataract extraction in eight eyes. One eye had a history of nonpenetrating trauma and lens dislocation. In one eye a retinal tear was noted intraoperatively and treated. Six eyes had postoperative visual acuity of 20/50 or better. In all eyes the lens was removed without further complications. Perfluorocarbon liquids such as perfluorophenanthrene may enhance current techniques by allowing easier and safer removal of displaced lens fragments through the pars plana.

Cataract Extraction↗
PubMed1993

The perioperative morbidity of scheduled cesarean hysterectomy.

OBJECTIVE: To compare the outcomes of patients undergoing scheduled cesarean hysterectomy with those of women treated with cesarean delivery and subsequent hysterectomy. METHODS: Through a retrospective review of 43 patients, we investigated the morbidity associated with scheduled cesarean hysterectomy and compared these findings with the combined morbidity of scheduled cesarean delivery and subsequent abdominal hysterectomy in a control population. Controls were included only if the subsequent hysterectomy was performed within 3 years of the index cesarean delivery. Each study subject was assigned two controls matched for age, parity, number of previous cesarean deliveries, and indications for procedures. The incidence of the following major morbidity events was compared between the groups: transfusion, urinary tract injury, fistula formation, cellulitis or endometritis, postoperative abscess or hematoma formation, ileus, pneumonia, and wound complications requiring prolonged therapy (seroma, hematoma, infection). RESULTS: The number of women receiving transfusions after scheduled cesarean hysterectomy was greater than among controls (39.5 versus 15.1%; P < .05). The proportion of patients with major morbidity, exclusive of transfusion, was significantly greater in the control population (44%) than in women with scheduled cesarean hysterectomy (16%) (P < .05). The cumulative number of women with a major complication, such as transfusion or a morbid event, was 22 of 43 in the study group versus 44 of 86 in the control population, a nonsignificant difference. CONCLUSION: We found no significant difference in the cumulative perioperative complication rates in women undergoing scheduled cesarean hysterectomy compared with a population of similar patients treated with cesarean delivery and subsequent abdominal hysterectomy.

Adult↗
PubMed1993

Postmortem localization of HIV-1 RNA by in situ hybridization in lymphoid tissues of intravenous drug addicts who died unexpectedly.

The histopathological alterations in lymphoid tissues and the presence of human immunodeficiency virus (HIV-1) RNA were studied in 25 consecutive autopsies of seropositive, apparently asymptomatic, intravenous drug overdose victims without palpable lymphadenopathy. The majority of lymphoid tissues in a given person showed either a combination of follicular hyperplasia and fragmentation or a combination of involution and depletion. Individuals with involuted and depleted lymphoid tissues were significantly older than those individuals with hyperplasia and fragmentation of follicles. Lymph nodes from individuals with hyperplasia with or without fragmentation were slightly but significantly larger than control nodes from seronegative persons. In tissues from infected cases, HIV-1 RNA was demonstrated by in situ hybridization in 49% of follicular centers showing hyperplasia, 62% of hyperplastic fragmented follicles, and 66% of involuted follicles in a distribution of follicular dendritic cells. No signal was detected in tissues demonstrating follicular depletion or nodes from seronegative persons. Scattered inter- and intrafollicular lymphoid cells with positive signal were present only in nodal tissues with follicular hyperplasia without involution. Tonsils, inguinal, axillary, mediastinal, supraclavicular, mesenteric nodes, and spleen were positive for HIV-1 RNA in 78%, 76%, 67%, 65%, 58%, 50%, and 28% of cases, respectively, and the prevalence of positivity reflected the presence of follicles. We conclude that the clinically asymptomatic period of HIV-1 infection is characterized by pathological stages in lymphoid tissues that have distinct histological alterations and distribution of viral RNA.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Sudden retinal manifestations of intranasal cocaine and methamphetamine abuse.

We examined two patients who had sudden decrease in vision after intranasal cocaine or methamphetamine abuse. A 38-year-old woman with a history of systemic arterial hypertension developed a central retinal artery occlusion four hours after intranasal use of cocaine. A 26-year-old woman had blurred vision and intraretinal hemorrhages shortly after using methamphetamine nasally. The adrenomimetic response and sudden increase in blood pressure associated with the intranasal use of these drugs may have contributed to the retinal vascular manifestations observed in these patients.

Cocaine↗
PubMed1990

Recurrent epistaxis, chronic pancytopenia and nasal mycosis.

A 52-year-old man with chronic, profound pancytopenia associated with a four-year history of Waldenstrom's macroglobulinemia refractory to chemotherapy began to experience major epistaxes requiring hospital admission for control. A diagnosis of invasive Aspergillus was made on nasal mucosal biopsy. A regimen of bi-weekly intravenous and sixth-hourly topical amphotericin B drops with adjuvant rifampicin successfully eradicated local nasal pain as well as the epistaxis. Resolution of infection was documented by gallium scan. It is suggested that, in addition to the aggressive craniofacial mycoses already described, lower grade nasal mycoses occur. The roles of biopsy and gallium scan in immunocompromised hosts with epistaxis are discussed.

Aspergillosis↗
PubMed1989

A randomised trial of empirical antibiotic therapy in febrile neutropenic patients with hematological disorders: ceftazidime versus azlocillin plus amikacin.

One hundred and two patients with neutropenia (less than 1 x 10(9)/L) secondary to primary hematological disorders or chemotherapy for hematological malignancies were prospectively randomised, upon the development of fever or other signs of infection, to receive empirical antibiotic treatment with either ceftazidime (+/- flucloxacillin) (n = 52) or azlocillin plus amikacin (+/- flucloxacillin) (A&A, n = 50). The two groups were equivalent with respect to clinical and laboratory parameters prior to antibiotic therapy and flucloxacillin was added to approximately 25% of the patients in each group on the clinical suspicion of Gram positive infection. When assessed at 96 hours, the complete response rates were 59.6% for the ceftazidime treated patients and 44% for A&A treated patients. Partial response rates were 17% and 20% respectively. This difference was not statistically significant. Eight patients died whilst on the trial, three of those initially randomised to ceftazidime and five initially randomised to A&A. Moderate to severe hypokalemia was encountered significantly less often in the ceftazidime treated group (p less than 0.01), whilst other parameters of toxicity were equivalent. No primary or acquired resistance to ceftazidime was encountered. Separate analysis of those patients who did not receive flucloxacillin yielded identical results. We conclude that ceftazidime (+/- flucloxacillin) is as efficacious as azlocillin plus amikacin (+/- flucloxacillin) in the empirical antibiotic management of such patients and is associated with a lower incidence of moderate to severe hypokalemia.

Adolescent↗
PubMed1987

Cryotherapy for active retinopathy of prematurity.

Twenty-eight patients with bilateral symmetrical stage-III retinopathy of prematurity and plus disease had one eye treated using cryotherapy, while the other acted as a control. Eleven patients showed improvement in both the treated and untreated eye, while 11 others were noted to improve in the treated eye while demonstrating deterioration in the untreated eye. The P value obtained by applying binomial distribution tests suggested that, in the sampled population, cryotherapy was preferable to no treatment.

Clinical Trials as Topic↗
PubMed1985

Carotid sinus hypersensitivity: evaluation of the vasodepressor component.

The basis of the vasodepressor response in patients with carotid sinus hypersensitivity (CSH) is unknown, and prevention of recurrent vasodepressor-induced hypotension in these patients has not been possible. In this study we assessed the effectiveness of atrioventricular sequential pacing and pharmacologic interventions in the prevention of carotid sinus massage (CSM)-induced vasodepressor responses in eight patients with CSH. Maintenance of constant heart rate (80 beats/min) and atrioventricular synchrony (atrioventricular interval 150 msec) with sequential pacing did not significantly alter mean CSM-induced fall in systolic pressure (CSM control, -60 +/- 12 mm Hg vs CSM with atrioventricular sequential pacing, -48 +/- 19 mm Hg). Similarly, neither pharmacologic muscarinic blockade nor combined muscarinic and beta-adrenergic blockade significantly attenuated CSM-induced fall in systolic pressure (CSM with atropine, -43 +/- 16 mm Hg; CSM with atropine plus propranolol, -47 +/- 18 mm Hg; both p = NS vs atrioventricular sequential pacing alone). On the other hand, intravenous norepinephrine and oral ephedrine blunted the CSM-induced drop in systolic pressure (CSM with norepinephrine, -19 +/- 12 mm Hg; CSM with ephedrine, -21 +/- 11 mm Hg; both p less than .01 vs atrioventricular sequential pacing alone). Thus, vasodepressor responses were not prevented by control of heart rate, maintenance of atrioventricular synchrony, pharmacologic muscarinic blockade, or combined muscarinic and beta-adrenergic blockade, but were attenuated by drugs believed to be predominantly alpha-adrenergic agonists. Consequently, atrioventricular sequential pacing alone may be inadequate to prevent hypotension in patients with pronounced vasodepressor responses, whereas administration of vasoconstrictors such as ephedrine may diminish symptoms.

Aged↗
PubMed1985

Atrial flutter in infancy: diagnosis, clinical features, and treatment.

The clinical features and treatment of atrial flutter in eight infants (four male and four female) less than 2 months of age are presented. Atrial flutter was noted during the first week of life in six of the infants and between 6 and 8 weeks of life in the other two infants. Four of the eight infants had associated structural or functional cardiovascular disease, and in three infants a central venous pressure catheter was present in the atrium at the time atrial flutter was diagnosed. Classic flutter waves were apparent on 12-lead ECGs in only two infants. In six infants, flutter waves were not obvious on standard ECGs, but transesophageal electrogram recordings demonstrated the presence of atrial flutter with second degree atrioventricular block. The atrial cycle length during flutter ranged from 135 to 180 ms (mean 149 ms; mean atrial rate 403 beats per minute); there was a 2:1 ventricular response to atrial flutter. Successful termination of atrial flutter was accomplished using three modes of electrical cardioversion in seven of the eight infants: direct current cardioversion in one, transvenous atrial pacing in one, and transesophageal atrial pacing in five. One asymptomatic infant converted to normal sinus rhythm 24 hours following digoxin administration. One infant had multiple atrial flutter recurrences and required chronic procainamide therapy. In seven of the eight infants, no recurrences have been noted in 6 months to 3 1/2 years of follow-up. These results demonstrate that atrial flutter may be difficult to diagnose in infants with tachycardia unless transesophageal electrogram recording is utilized for evaluation.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial Flutter↗