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Biomedical subjects

A Shapiro

Publications and source records attributed to A Shapiro.

At least 91 records · Page 5Linked to original sources
PubMed1997

Increase in surface expression of ICAM-1, VCAM-1 and E-selectin in human cerebromicrovascular endothelial cells subjected to ischemia-like insults.

Secondary ischemic brain injury has been shown to develop as a consequence of inflammation and vasogenic brain edema. In this study we show that inflammatory cytokines and simulated in vitro ischemia stimulate the surface expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and endothelial-leukocyte adhesion molecule-1 (E-selectin) in human cerebromicrovascular endothelial cells (HCEC) in culture. The levels of all three adhesion molecules were dramatically (3 to 10-fold) up-regulated by 4-24 hour exposure to the inflammatory cytokines. IL-1 beta (10-200 u/ml) or TNF alpha (50 200 u/ml), and by a 4 hour exposure to "simulated" in vitro ischemia, as determined by immunocytochemistry and ELISA. Following 24 hours of subsequent reperfusion, the expression of ICAM-1 and VCAM-1 was maintained at ischemia-induced levels, whereas E-selectin was no longer detectable. Both the cytokine- and ischemia-induced up-regulation of adhesion molecules were completely abolished by the transcriptional inhibitor, actinomycin D (10 micrograms/ml), and inhibited by the cycloxygenase (COX) inhibitor, indomethacin (300 microM). These findings implicate HCEC in the processes of leukocyte adhesion and recruitment in the brain during stroke in vivo.

Brain Ischemia↗
PubMed1997

Complete staghorn calculi: random prospective comparison between extracorporeal shock wave lithotripsy monotherapy and combined with percutaneous nephrostolithotomy.

PURPOSE: We determined the preferred treatment of staghorn calculi. MATERIALS AND METHODS: Between January 1992 and December 1994 we performed a prospective, randomized, single center study involving 50 kidneys with complete staghorn calculi: 27 renal units were treated with extracorporeal shock wave lithotripsy (ESWL) monotherapy (group 1) and 23 were treated with combined (initial) percutaneous nephrostolithotomy with ESWL (group 2). The 2 treatment groups were compared regarding stone size, grade of collecting system dilatation and urine culture at presentation. The number of treatment sessions, narcotic doses, renal colic episodes, septic complications, unplanned ancillary procedures, length of hospitalization, total treatment duration and stone-free rate at 6 months were recorded and compared. RESULTS: At the conclusion of therapy the stone-free rate was significantly greater in group 2 than in group 1 (74 versus 22%, respectively, p = 0.0005). The complication rate was significantly greater in group 1, with 15 septic complications (fever greater than 38.5C for longer than 3 days) in 10 patients compared to only 2 episodes in group 2 (p = 0.007). The unplanned ancillary procedure rate was significantly greater in group 1 (8 procedures in 7 patients versus 1 procedure in group 2, p = 0.03). The overall treatment length was significantly shorter in group 2 (1 versus 6 months, p = 0.0006). There was no significant difference in the number of procedures performed with anesthesia or in the number of hospitalization days between the 2 treatment groups. CONCLUSIONS: Combined percutaneous nephrostolithotomy and ESWL should be recommended as the first line treatment choice for most patients with staghorn stones.

Adult↗
PubMed1997

The induction of ICAM-1 in human cerebromicrovascular endothelial cells (HCEC) by ischemia-like conditions promotes enhanced neutrophil/HCEC adhesion.

Ischemic brain injury is exacerbated by leukocyte infiltration and formation of vasogenic edema. In this study we demonstrate that intercellular adhesion molecule-1 (ICAM-1) is dramatically (3 to 15-fold) up-regulated in human cerebromicrovascular endothelial cells (HCEC) by a 16 h exposure to the cytokine, IL-1 beta (50-200 u/ml), the phorbol ester, TPA (1-100 nM), or by simulated in vitro ischemia/reperfusion. These treatments also significantly increased the adhesion of allogeneic neutrophils to HCEC monolayers. Both IL-1 beta- and TPA-induced expression of ICAM-1 and increased neutrophil adhesion to HCEC were inhibited by the transcriptional inhibitor, actinomycin D (AcD; 1-10 micrograms/ml), and by an anti-ICAM-1 antibody (ICAM-1 Ab). By contrast, ischemia-induced neutrophil adhesion was only slightly affected by AcD and ICAM-1 Ab alone, but it was abolished by the combination of anti-ICAM-1 and anti-CD18 antibodies. The increase in surface expression of ICAM-1 and neutrophil adhesion by IL-1 beta, TPA and ischemia were significantly reduced by the cyclo-oxygenase (COX) inhibitors, indomethacin (100-300 microM) and dexamethasone (10-50 microM). These results indicate that ICAM-1 expression in HCEC can lead to enhanced neutrophil adhesion and that COX activation in HCEC likely plays a role in the processes by which leukocyte adhesion and recruitment take place in the brain during inflammation and ischemia in vivo.

Blood-Brain Barrier↗
PubMed1997

Anxiety and patient participation in clinical decision-making: the case of patients with ureteral calculi.

Ninety-six patients with a ureteral calculus participated in a study whose purpose was to identify those subjects who would benefit from participation in clinical decision-making. Forty-two of the subjects (the experimental group) were given information about two alternative treatments, Extra Corporeal Shock Wave Lithotripsy (ESWL) and ureteroscopy, and were asked to choose which therapy they preferred. Fifty-four subjects (the control group) were not given information, not allowed to choose, and were treated according to the physician's decision. Subjects' level of anxiety was compared within each group on three occasions: before meeting with the physician, immediately afterwards and upon hospitalization for treatment of the stone. Patients perception of receipt of information and participation in clinical decision-making, coping style, educational level, and knowledge about treatment alternatives were also measured. A statistically significant decrease in anxiety after meeting with the urologist was found among patients who were not asked to participate in the decision-making process and among patients who perceived that they had received information. A decrease in anxiety after meeting with the physician was also found among patients who, according to their own perception, did not participate in decision-making. Patients' educational level and coping style were related to their anxiety. A decline in anxiety was found among those with a lower educational level who perceived that they had received information and among higher educated patients who perceived that they participated in clinical decision-making. Anxiety also declined among patients with a passive coping style who perceived that they had received information or had participated in the decision-making process. The results emphasize the need to tailor the therapeutic approach to patient characteristics.

Adolescent↗
PubMed1997

Acute normovolaemic haemodilution decreases postoperative allogeneic blood transfusion after total knee replacement.

We hypothesized that the success of postoperative blood conservation after acute normovolaemic haemodilution (NVHD) is influenced by the extent of intraoperative bleeding and surgical trauma, and the timing of autologous blood transfusion. As total knee replacement is associated with minimal intraoperative but extensive postoperative blood loss, this procedure is ideally suited to acute NVHD. Therefore, to test our hypothesis, 30 patients undergoing elective total knee replacement were enrolled in a prospective, randomized, controlled study. In groups NVHD-2 and NVHD-6, before induction of anaesthesia patients were bled to a target packed cell volume (PCV) of 28-30%, and in the post-anaesthesia care unit autologous blood was transfused over a 2-h period terminating after operation at 2 and 6 h, respectively. In the control group, NVHD was not performed. After operation, platelets, fibrinogen, prothrombin and partial thromboplastin time, and liver function, urea and electrolytes were measured and compared with preoperative baseline values. Significantly (P < 0.024) more allogeneic blood was transfused in the control group (21 u.) compared with either group NVHD-2 (7 u.) or group NVHD-6 (5 u.). In the control group, despite the allogeneic blood transfusion, postoperative PCV decreased until day 4 after operation. Coagulation profile, liver function and urea and electrolytes concentrations were unaffected by the method of treatment. We conclude that for total knee replacement, acute NVHD is an effective blood conservation strategy. However, there was no difference in allogeneic blood administration between the two NVHD groups. Coagulation and liver function, and urea and electrolyte concentrations were unaffected by treatment.

Aged↗
PubMed1997

Restoration of the patency of the nasolacrimal drainage system.

The anatomical lacrimal drainage system was restored in 30 patients who suffered from dacryostenosis and tearing. Previously, in order to alleviate these patients' symptoms, a dacryocystorhinostomy had had to be performed. In the new procedure, local anesthesia was given, and a 600-micron fiberoptic was introduced through the lacrimal drainage system to the obstruction area. A continuous 20 W/s Neodymium:YAG laser energy was used to reopen the drainage system. This is a simple office procedure. No skin cuts are required, no anatomical changes are made, and there is practically no bleeding. All patients returned to their normal everyday activity within a few hours after the procedure.

Aged↗
PubMed1997

Lack of association between hearing loss and glaucoma.

Some studies have suggested a relationship between glaucoma and sensorineural hearing loss. Others have found no evidence for an association. We performed a study to determine whether there is a significant difference in hearing between patients with glaucoma and a matched control population. Patients presenting themselves to a glaucoma clinic were grouped by type of glaucoma: uveitis, primary open-angle, pigmentary, pigmentary dispersion, congenital, or ocular hypertension. Patients older than 60 were excluded from the study, as were those who met certain carefully chosen exclusion criteria. Subjects included 40 men and 27 women, ranging in age from 15 to 60 years. Glaucoma was bilateral in all cases. Auditory thresholds at 0.5, 1.0, 2.0, and 3.0 kHz were measured bilaterally and statistically compared with American National Standards Institute (ANSI) normative values. Speech reception threshold and intelligibility were also assessed. When compared with speech ANSI values, there were no significant differences in mean thresholds at any frequency for any of the glaucoma types. Mean speech reception thresholds and intelligibility scores were all within normal limits and no subjects showed evidence of sensorineural hearing loss greater than expected for age. There were no differences between glaucoma groups, and we found no evidence of an association between glaucoma and hearing loss. There is disagreement about whether or not an association exists between glaucoma and hearing loss. Among those who do feel there is a relation, there is wide disagreement about what proportion of glaucomatous patients have a hearing loss. Rampoldi (1) first described an association between glaucoma and inner ear disease in 1889. Since that time, a number of reports have suggested such an association (2-4; 6-12). However, many of these studies are methodologically flawed. A few studies found no evidence of a relationship between glaucoma and sensorineural hearing loss (14, 15). There have been few reports since the 1970s, and the question remains unresolved. If there is, in fact, a relationship between glaucoma and inner ear disease, potentially much could be learned about certain forms of hearing loss from the study of glaucoma. In particular, surgical specimens (trabecular meshwork) could be obtained in those patients who undergo operations for their glaucoma. This tissue could be examined using current histopathological techniques. On the basis of the results, hypotheses might be made, by inference about which pathological processes are manifested in the inner ear. Therefore, we performed a study to evaluate whether there is a significant difference in hearing between patients with glaucoma and a matched control population.

Adolescent↗
PubMed1997

[Radical retropubic prostatectomy].

Radical prostatectomy may cure most patients in whom the malignant tumor has not invaded through the prostatic capsule. Advances in surgical technique and accumulation of experience have decreased the complication rate significantly. Long-term results of surgical treatment are now better than those of other forms of treatment; hence radical prostatectomy is now recommended for men with life expectancies longer than 10 years. Between 1988 and 1995, 164 men with clinical stages T1 or T2 adenocarcinoma were admitted for radical prostatectomy. Most were not offered a nerve-sparing procedure, so as to allow wider, more complete resection. Those who wanted preservation of sexual function underwent the nerve- preserving procedure. In 6 patients operation was discontinued when metastases to the mac lymph nodes were detected and in 1 when invasion of the pelvic wall was found, 157 underwent radical prostatectomy. Preoperative biopsy revealed a low-grade lesion (Gleason 2-4) in 19.1%, intermediate grade (Gleason 5-6) in 61.8% and high-grade (Gleason 7-9) in 19.1%; however, pathologic grading revealed that only 7.0% had grade 2-4 tumor, 60.5% grade 5-6 and 32.5% grade 7-9. Pathologic staging revealed T2 tumor in 58%, T3 in 38.8% (including microscopic invasion of the capsule or seminal vesicles); microscopic lymph node metastases were found in 3.2%. Tumor invasion through the capsule was found in only 2 of 13 treated with neoadjuvant androgen blockade, compared with 40% in those who did not receive this treatment. There was no operative mortality and only 14.7% has complications. All had urinary incontinence immediately after operation, but regained continence after an average of 4-5 months, 24 were incontinent for more than 12 months, but most of them had only mild stress incontinence. Most patients were impotent after the procedure. There was tumor recurrence, diagnosed by rise in serum PSA, in 26 during an average followup of 26.4 months (range 3-93). Cure rate of prostatic cancer by radical prostatectomy may be increased by improved preoperative staging methods and better patient selection; long term follow up is required for determining cure rate.

Aged↗
PubMed1996

Topological folding and proteolysis profile of P-glycoprotein in membranes of multidrug-resistant cells: implications for the drug-transport mechanism.

P-glycoprotein (Pgp)1 is a polytopic membrane protein and functions as an energy-dependent drug efflux pump. It is responsible for multidrug resistance (MDR) in cancer cell lines. Recently, the topological structure of Pgp has been investigated. However, the results are in dispute. A major question concerning the Pgp topology is the membrane orientation of the loop linking TM4 and TM5 (loop 4) and the loop linking TM8 and TM9 (loop 8). In this study, we generated polyclonal antibodies specific to these two loops. In combination with a panel of other well-characterized site-specific polyclonal- and monoclonal antibodies of Pgp, we tested the membrane orientation of these two loops of Pgp in multidrug-resistant cells using immunocytochemistry and proteolysis/membrane protection assay. Our results showed that (1) both loops 4 and 8 are located extracellularly whereas other domains, such as the ATP-binding sites, are in the cytoplasm and (2) proteolysis of Pgp is not a random event and the trypsin-sensitive sites are cleaved in orders. Since the Pgp was not genetically manipulated in this study, in contrast to previous studies, we believe that naturally expressed Pgp molecules have an unconventional topology. We speculate that this alternate topology of Pgp may represent a different functional state of the protein. Further detailed analysis of Pgp topology will help to understand the fundamental mechanism of drug transport by Pgp.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Uterine polypoid hemangioendothelioma: conservative treatment.

BACKGROUND AND OBJECTIVE: A polypoid uterine hemangioendothelioma was treated by conservative means. STUDY DESIGN/MATERIALS AND METHODS: The diagnosis of hemangioendothelioma was confirmed by histopathology and angiography. The patient desired to retain her fertility; therefore, the hemangioendothelioma was treated by hysteroscopically guided Nd:YAG laser ablation. RESULTS: Five years of follow-up by hysteroscopy and dilation and curettage reveal no evidence of recurrence. The patient continues to have regular menses. CONCLUSION: Conservative management of a uterine hemangioendothelioma by Nd:YAG laser ablation was successful over 5 years of follow-up.

Adult↗
PubMed1996

Prediction of response to treatment in superficial bladder carcinoma through pattern of interleukin-2 gene expression.

PURPOSE: Superficial bladder carcinoma, treated by resection and intravesical administration of bacillus Calmette-Guérin (BCG), yields a remission rate that approaches 70%. We examined whether expression of interleukin-2 (IL-2) or interferon-gamma (IFN-gamma) genes can serve to predict response. PATIENTS AND METHODS: During BCG treatment, we analyzed induction of IL-2 and IFN-gamma mRNA in peripheral-blood mononuclear cells (PBMC) from 73 patients: 51 with papillary tumors and 22 with carcinoma-in-situ (CIS). Results were correlated with remission, relapse, or tumor persistence over a 4-year follow-up period. RESULTS: Independent of tumor type, induction of IL-2 mRNA was observed for patients who responded with remission, but not for those who relapsed (P = .0001). Multivariate logistic analysis showed that inducibility of IL-2 mRNA is the discriminating parameter, which yields a predictive value of 97% for remission. Of 23 patients with relapse/persistence, 22 lacked inducibility of IL-2 mRNA (sensitivity, 95.6%), while 35 of 50 patients in remission exhibited inducibility (specificity, 70%). For patients with carcinoma-in-situ, in which remission or failure depends solely on response to BCG, sensitivity and specificity were 88% and 86%, respectively; for patients with papillary tumors, they were 100% and 64%. IFN-gamma mRNA, by contrast, was clearly inducible in PBMC from all patients (P = .51). The disease-free interval increased progressively with inducibility of IL-2 mRNA; this trend was highly significant (P = .0001). CONCLUSION: IL-2 gene expression is essential for mounting an antitumor response in superficial bladder carcinoma. Inducibility of IL-2 mRNA is an independent prognostic parameter and useful predictive indicator of remission versus relapse.

Adjuvants, Immunologic↗
PubMed1995

The impact of different types of anesthesia on in vitro fertilization-embryo transfer treatment outcome.

OBJECTIVE: Our objective was to evaluate retrospectively the influence of different types of anesthesia on the outcome of ovum retrieval. METHODS: Sedation combined with local anesthesia was used on 120 occasions (Group I), epidural block in 139 ovum retrievals (Group II), and general anesthesia in 173 cycles (Group III). RESULTS: No differences were found in embryo yield or number or the quality of the embryo transferred. Of 99 pregnancies achieved, 66 live deliveries were recorded. Significantly lower clinical pregnancy rates were found in Group III (14.5%) compared with Group II (23.7%; P = 0.018) or Group I (25.8%; P = 0.0074). Highly significant differences were found in the delivery rates between Group III (8.7%), Group II (20.11%; P = 0.0017), and Group I (19.2%; P = 0.0043). CONCLUSION: The use of general anesthesia, especially nitrous oxide, for oocyte retrieval has an adverse effect on IVF outcome. This deleterious effect manifests itself only after embryo transfer and leads to lower pregnancy and delivery rates.

Adult↗
PubMed1995

Detection of bladder tumors by immunostaining of the Lewis X antigen in cells from voided urine.

OBJECTIVES: A study was made to determine the sensitivity and specificity of immunostaining of the Lewis X antigen in exfoliated urothelial cells from voided urine, for the detection and surveillance of bladder tumors. METHODS: Three consecutive voided urine specimens were obtained from 101 patients, 78 of whom were under surveillance because of a history of bladder tumors, and 23 were being evaluated because of hematuria or irritative urinary symptoms. Indirect immunoperoxidase staining of two urine samples was done on cytocentrifuge slides, using the P12 monoclonal antibody against the Lewis X antigen. The diagnosis of the presence of urothelial tumor was made if more than 5% of the cells showed a typical red-brown staining. Cytopathologic examination of the third urine specimen was done according to Papanicolaou. Each patient underwent cystoscopy, and biopsies were obtained whenever there was endoscopic evidence of bladder tumors or carcinoma in situ. RESULTS: Cystoscopy and biopsies revealed transitional cell carcinoma in 32 patients, whereas 69 patients had no evidence of bladder tumors. Immunocytology of one urine sample showed true-positive results in 26 of the 32 patients with bladder tumors, corresponding to a sensitivity of 81.25%. When two samples were examined, a sensitivity of 97% and a specificity of 85.5% were obtained. When the results of cytology and immunocytology were combined, sensitivity reached 100%. High-grade and low-grade transitional cell tumors were detected with equal efficiency. CONCLUSIONS: The use of P12 monoclonal antibody for evaluation of Lewis X reactivity in cytologic preparations from multiple voided urine specimens can improve the sensitivity of noninvasive detection of bladder cancer. The technique may ultimately replace cystoscopy in monitoring therapeutic response and tumor recurrence.

Biomarkers, Tumor↗
PubMed1995

Low risk of viral infection after administration of vapor-heated factor VII concentrate or factor IX complex in first-time recipients of blood components. International Factor Safety Study Group.

BACKGROUND: Vapor-heated human factor VII concentrate and human factor IX complex are both obtained from prothrombin complex, undergo similar methods of manufacture, and are subjected to an identical two-step vapor-heating process for virus inactivation. STUDY DESIGN AND METHODS: Intermediate-purity vapor-heated human factor VII concentrate and vapor-heated human factor IX complex were monitored for safety with regard to viral infection in the context of an International Factor Safety Study, a prospective study that follows the revised recommendations from the International Congress of Thrombosis and Hemostasis (ICTH). Because the rarity of the respective hereditary deficiencies would have made separate analyses unrealizable, the results were combined for the final analysis. Entry required that patients have no history of transfusion with any blood derivative. After the first infusion of the study drug, patients were monitored for 6 months for the development of non-A, non-B hepatitis (NANBH) and infection with hepatitis B virus (HBV) and for 15 months for infection with hepatitis C virus (HCV) and human immunodeficiency virus (HIV). An event was defined as a positive result on any test for any infection. An alanine aminotransferase level more than 2.5 times the upper limit of normal on two consecutive occasions was defined as an event for NANBH. HBV infection was monitored with tests for three different HBV markers: the HBV surface antigen, antibody against the HBV surface antigen, and antibody against HBV core antigen. HCV and HIV infection were monitored with tests for HCV and HIV antibodies. RESULTS: The 25 patients who completed the study (1 has not completed the study and 1 dropped out) received a total of 434 infusions comprising 17 different production lots of the concentrates. Twenty patients were analyzable for NANBH and 25 for HCV and HIV infection. Since most patients had been given HBV vaccination, only 4 patients were analyzable for this end point. None of the patients showed evidence of having developed an event. These data satisfy ICTH criteria when the products are considered together, but vapor-heated factor VII concentrate does not qualify alone because there were only five patients in this group. CONCLUSION: Vapor-heated factor VII concentrate and vapor-heated factor IX complex are associated with a low risk of viral infection. Preliminary results are also presented, indicating that the concentrates are safe with regard to inhibitor development.

Adult↗
PubMed1995

Calcium metabolism and requirements of chickens are affected by growth.

The interaction between growth and calcium homeostasis was studied by comparing the responses of (a) fast-growing broiler chickens (Cobb) and slow-growing Leghorns, and (b) fast-growing chickens (Cobb) fed either high energy (12.13 kJ/g) or low energy (9.2 kJ/g) diets, to dietary calcium concentration ranging between 4 and 20 g/kg). Plasma calcium increased as dietary calcium increased, reaching an apparent plateau between 0.8 and 1.5% dietary calcium, regardless of basal growth rate. Dietary calcium levels of 1.5% and higher induced hypercalcemia and hypophosphatemia in fast- but not in slow-growing chickens. Weight gain was unaffected by dietary calcium in the slow-growing Leghorns, but followed a bell-shaped response pattern in the fast-growing Cobb chickens. Growth inhibition by feeding of low energy diets changed the response pattern from a quadratic form to that of an increase towards a plateau. The response of bone ash to dietary calcium was characterized as quadratic in fast-growing chicks, changing to a pattern of increase towards a plateau in slow-growing chicks. Intestinal calbindin was suppressed by dietary calcium and was higher in the fast-growing than in the slow-growing chicks. An increase in dietary phosphorus resulted in a shift in the response curves of weight gain and bone ash and an increase in the calcium requirements. The results indicate that the response of chicks to dietary calcium and calcium requirements is markedly modified by growth rate.

Analysis of Variance↗
PubMed1995

[Cystinuria and urolithiasis].

Cystinuria is a hereditary metabolic disorder which causes urinary lithiasis. Patients with cystinuria present at an earlier age (17 years), and with larger stones than patients with other types of urinary stones. As a result of frequent formation of new stones and multiple operations, many patients suffer from obstructive nephropathy and deterioration of kidney function. During the past decade we treated and followed 51 patients with cystine urolithiasis from 39 families. Screening disclosed another family member with cystinuria in 56% of the cases. The diagnosis of cystinuria was only made an average of 2 years after a patient first presented. In the group 12 kidneys had been removed due to various complications and in 7 kidneys there was significant deterioration of function. Each patient underwent a mean of 5.8 surgical interventions, including open operations, extra-corporeal shock wave lithotripsy (ESWL), percutaneous nephrolithotripsy (PCNL) and urethroscopy, but most still had residual stone fragments. To prevent complications from cystine urolithiasis every effort should be made to detect the disease early, including screening of families of patients with cystinuria and close follow-up of all family members. Early detection of stones, before they become large makes noninvasive treatment with ESWL possible, whereas large stones require PCNL. Patients should be urged to maintain high urine outputs and to continue uninterrupted treatment with penicillamine or tiopronin, and urinary alkalinization.

Cystinuria↗
PubMed1994

A multicenter study of recombinant factor VIII (recombinate): safety, efficacy, and inhibitor risk in previously untreated patients with hemophilia A. The Recombinate Study Group.

In July 1990, the Recombinate Study Group initiated a prospective, open-labeled investigation of recombinant factor VIII (r-FVIII) to assess its safety and efficacy and to characterize the natural history of inhibitor development in previously untreated patients (PUPs) with hemophilia A. All study subjects have severe FVIII deficiency (baseline FVIII level < or = 2% of normal) and no history of blood product exposure before study entry. Following the first r-FVIII infusion, plasma was screened for inhibitors once every 3 months, and plasma recovery of r-FVIII at 30 minutes and 24 hours postinfusion was assayed at least once every 6 months. As of May 1993, 73 of 79 patients originally enrolled in the trial continue to participate. The median number of r-FVIII exposure-days for the 71 subjects who have received at least one r-FVIII infusion is 11. A total of 1,785 infusions have been administered to treat 810 bleeding events. Ninety-two percent of bleeding events responded as anticipated to one or two infusions. Two, nonrecurring, acute adverse reactions occurred coincident with r-FVIII infusion, one of which was unrelated and the other, possibly related to the infusion. Seventeen (23.9%) subjects have developed inhibitors: five with peak titers more than 10 Bethesda units (BU) and 12 with peak titers < or = 10 BU (range, 0.5 to 10). Survival analysis showed that the probability of remaining inhibitor-free in this group of patients with severe hemophilia A is 88.4% after 8, 73.6% after 10, and 61.6% after 25 r-FVIII exposure-days. Inhibitors disappeared in five (29.4%) subjects on retesting 2 to 16 months after the last positive inhibitor assay. r-FVIII is safe and effective in the treatment of hemophilia A-related bleeding. To date, the inhibitor risk associated with its use is comparable to that in patients treated with plasma-derived concentrates. The majority of inhibitors identified are low in titer and do not preclude continued on-demand therapy with r-FVIII.

Antibodies↗