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Biomedical subjects

P M Falk

Publications and source records attributed to P M Falk.

At least 19 recordsLinked to original sources
PubMed2006

Maintenance thalidomide following single cycle autologous peripheral blood stem cell transplant in patients with multiple myeloma.

Although autologous stem cell transplant is an effective therapy for patients with multiple myeloma and extends progression-free survival (PFS) and overall survival (OS), patients show a continued pattern of recurrent disease. Twenty-nine patients were enrolled in a phase II study investigating the tolerability and efficacy of maintenance thalidomide following single autologous peripheral blood stem cell transplant. Six to eight weeks after transplant, patients were started on maintenance thalidomide at 50 mg a day. The dose was gradually escalated to a target dose of 400 mg a day and continued until disease progression or 6 months after achieving complete remission (CR) for a maximum total duration of 18 months. At 6 months, 13 patients (45%) achieved CR or near complete remission (positive immunofixation without any evidence of disease). The estimated 2-year OS was 83% and PFS was 49%. Median tolerated dose of thalidomide was 200 mg a day. In conclusion, thalidomide as maintenance therapy is feasible and may improve outcome after single autologous stem cell transplant.

Aged↗
PubMed2004

Cyclosporine and mycophenolate mofetil prophylaxis with fludarabine and melphalan conditioning for unrelated donor transplantation: a prospective study of 22 patients with hematologic malignancies.

In an attempt to decrease toxicity in high-risk patients undergoing unrelated donor hematopoietic stem cell transplantation (URD HSCT), we tested a combination of cyclosporine (CSP) and mycophenolate mofetil (MMF) as graft-versus-host disease (GVHD) prophylaxis with the reduced-intensity conditioning regimen fludarabine/melphalan (Flu/Mel). A total of 22 adult patients with advanced myeloid (n=15) and lymphoid (n=7) malignancies were treated. All patients received Flu 25 mg/m2 for 5 days and Mel 140 mg/m2, with CSP 3 mg/kg daily and MMF 15 mg/kg three times a day. The median age was 49 years (range 18-66). Durable engraftment was seen in all but one patient with myelofibrosis. The 1-year nonrelapse mortality was 32%, 27% from GVHD. The cumulative incidence of acute GVHD grade 2-4 and 3-4 was 63 and 41%, respectively. With a median follow-up of 18 months, the disease-free survival (DFS) and overall survival (OS) are 55 and 59%, respectively. For patients with AML and MDS (n=14), the DFS and OS is 71%. For patients undergoing a second transplant (n=14), the DFS and OS is 57%. In conclusion, this regimen is associated with acceptable toxicity but high rates of GVHD in high-risk patients undergoing URD HSCT. Encouraging disease control for patients with advanced myeloid malignancies was observed.

Adolescent↗
PubMed1998

Ileoanal pouch function and release of peptide YY.

PURPOSE: This study evaluates peptide tyrosine-tyrosine (PYY), intestinal transit, fecal retention time, and anal sphincter manometry in colectomized patients with ileal pouch-anal anastomosis. METHODS: Plasma and pouch PYY, mouth-to-pouch transit time, fecal retention time, and anal canal pressures were studied in 27 patients with ileoanal pouches a mean of 50 (range, 3-84) months after loop ileostomy closure. RESULTS: Basal and peak postprandial plasma PYY were significantly reduced in patients with pouches compared with controls (P < 0.0001). Pouch PYY was decreased compared with control ileal PYY (P = 0.0003). No significant correlation was noted between intestinal transit and total integrated PYY response in patients with pouches (r=0.36; P=0.06). Fecal retention time was related to postprandial total integrated response of plasma PYY (r=0.43; P=0.02), mouth-to-pouch transit (r=0.87; P < 0.0001), and resting (r=0.44; P=0.02) and squeeze (r=0.62; P=0.0006) anal sphincter pressures. CONCLUSIONS: Colectomized ileoanal patients with pouches showed decreased plasma and pouch PYY compared with controls. Intestinal transit was not significantly related to PYY release. However, prolonged pouch fecal retention was associated with greater PYY release, mouth-to-pouch transit, and anal sphincter pressures.

Adolescent↗
PubMed1998

Pudendal nerve function in normal and encopretic children.

BACKGROUND: Abnormal pudendal nerve function contributes to fecal retention and incontinence in adults. To determine the role of pudendal neuropathy in childhood, we prospectively evaluated pudendal nerve function in normal and encopretic children. METHODS: We studied pudendal nerve terminal motor latency in 23 encopretic children and in an equal number of similarly aged, normal children. Anal manometry and electromyography were also obtained in all children. RESULTS: Pudendal nerve latency in the encopretic children equaled 1.58 +/- 0.33 msec, which was the same as that in control children. Of the 75 pudendal nerves tested, latency was prolonged in only one encopretic child. In contrast, anal electromyography demonstrated nonrelaxation of the external anal sphincter in 75% of the encopretic children but in only 13% of the normal children (p < 0.001). Anorectal manometry demonstrated, on average, lower and sphincter pressures at rest and with squeezing in the encopretic children (p < 0.01), but only 17% had sphincter pressures more than two standard deviations below normal. CONCLUSIONS: Other than poor relaxation response of the external anal sphincter during evacuation, these data reveal a paucity of functionally important abnormalities in encopretic children. In particular, we find no evidence that abnormal pudendal nerve function is important in the etiology or pathogenesis of encopresis in children.

Anal Canal↗
PubMed1997

Mucormycosis of the vulva following bone marrow transplantation.

Mucormycosis is uncommon in bone marrow transplant recipients. Primary cutaneous mucor in any setting is unusual. It may mimic necrotizing bacterial infection particularly in patients with severe neutropenia. We report a case of vulvar mucormycosis in a transplant recipient. Diagnosis depends on histological identification of fungal hyphae invading tissue and blood vessels.

Adult↗
PubMed1996

A comparison of single-dose and fractionated total-body irradiation on the development of pneumonitis following bone marrow transplantation.

PURPOSE: A review of 132 consecutive patients who received bone marrow transplant for various malignancies was conducted to determine factors associated with increased risk in developing interstitial pneumonitis (IP) as the result of total body irradiation (TBI). Twenty-four patients were excluded because 22 did not receive TBI and two had insufficient records. METHODS AND MATERIALS: Patients were conditioned with TBI and various drug regimens. Eighteen patients received a single 6.0 Gy dose of x-rays. The remaining 90 were treated with three doses of 3.33 Gy separated by 24 h. All patients were followed for at least 18 months for the purposes of determining the IP incidence. RESULTS: Twenty-seven of these 108 (25%) patients developed IP; 19 (17.6%) died. The 2-year estimated incidence of IP was 24 and 18.6% for fatal IP. The etiology was determined to be idiopathic in 12 patients, the result of cytomegalovirus in 6 patients, and caused by a variety of other infectious organisms in 9 patients. We were unable to demonstrate a statistically significant increase in IP with age (adults vs. children), dose regimen, use of methotrexate for graft-vs.-host disease prophylaxis, the presence of acute graft-vs.-host disease, time from diagnosis to transplant, or transplant type (allogeneic vs. autologous). CONCLUSIONS: The incidence of fatal IP reported here is similar to that reported by other institutions utilizing hyperfractionated TBI protocols. Our data do not support the need for hyperfractionation to reduce the risk of IP.

Adult↗
PubMed1996

Operative results of House advancement anoplasty.

A retrospective review of 29 patients who had an anoplasty using the sliding House advancement flap was carried out to evaluate the efficacy and safety of this new technique. Long-term symptom relief and late complications were determined by telephone interview. Indications for anoplasty were: stenosis (21 cases), ectropion (four), Bowen's disease (two), keyhole deformity (two) and perineal fistula (one). A single House flap was performed in most patients, but eight required multiple flaps. Lateral internal sphincterotomy was performed concomitantly in 16 of 21 patients with anal stenosis. Postoperative complications included donor-site separation (14), urinary retention (eight) and sepsis (four). At a median follow-up of 28 months, 26 of 29 patients had improved and 24 were completely satisfied. House flap anoplasty can be used to correct many anoderm deficiencies with a high rate of success and patient satisfaction.

Adult↗
PubMed1995

Response of the human hepatic tissue cultures Hep-G2 and WRL-68 to cocaine.

The hydrolytic metabolism of cocaine into benzoylecgonine, ecgonine methyl ester, and ecgonine was studied in the human hepatoma cell line Hep-G2 and in the nontumorigenic fetal hepatic cell line WRL-68. Also, the toxicological response of these cells to cocaine was compared to previously published results obtained with perfused liver cells and in vivo systems. Our experiments indicated that Hep-G2 appear to have similar metabolic and toxicological patterns to in vivo and perfused cell systems. The WRL-68 tissue culture system was found to be less similar. These results suggest Hep-G2 cells can be utilized to study cocaine metabolism and toxicology, and possibly in studies involving other xenobiotic compounds.

Carcinoma, Hepatocellular↗
PubMed1994

Positron emission tomography for preoperative staging of colorectal carcinoma.

PURPOSE: Positron emission tomography (PET) is an imaging technique based on in vivo cellular metabolism. Increased glucose metabolism in neoplastic cells is detected by using fluorine-18 deoxyglucose. In an ongoing pilot study to determine the usefulness of this technique, PET is compared with computerized tomography (CT) for the preoperative staging of colorectal carcinoma. METHODS: Sixteen patients were evaluated with both PET and CT of the abdomen and pelvis. Results were compared with operative and histopathologic findings. Fifteen malignant lesions were found in 16 patients by histology. PET had a positive predictive value of 93 percent and a negative predictive value of 50 percent. By comparison CT had a positive predictive value of 100 percent and a negative predictive value of 27 percent. CONCLUSIONS: These preliminary results indicate that PET has increased sensitivity for staging colorectal carcinoma, whereas CT has higher specificity. The predictive value of a positive PET compares favorably with CT. Furthermore, the predictive accuracy for detection of colorectal carcinoma is 83 percent for PET and 56 percent for CT.

Adult↗
PubMed1994

Transanal ultrasound and manometry in the evaluation of fecal incontinence.

PURPOSE: This preliminary study was undertaken to clarify the role of ultrasonography of anal sphincters in the colorectal laboratory. METHODS: Twenty-eight parous female patients with fecal incontinence were evaluated with transanal ultrasonography (TAUS), anal manometry, and pudendal nerve terminal motor latency (PNTML). Ultrasound images were recorded and labeled in centimeters from the anal verge. The continuity of the internal anal sphincter (IAS) was identified as either intact or disrupted. The separation of the external anal sphincter (EAS) was measured at the 1.5-cm level and below. TAUS findings were then compared with anal manometric pressures. Clinical data were obtained by patient interview and examination during TAUS. RESULTS: Evidence of IAS disruption was associated with significantly decreased mean maximum resting pressures (P = 0.023). EAS separation was inversely proportional to mean maximum squeezing pressures (r = -0.61). In the group of patients offered sphincteroplasty, the IAS was disrupted more often (P = 0.016), mean maximum resting pressures were significantly lower (P = 0.023), mean EAS separation was significantly greater (P = 0.022), and mean PNTML was significantly faster (P = 0.004). Twenty-five percent of patients with normal clinical examinations had significant muscular injury by TAUS requiring sphincteroplasty. CONCLUSIONS: Manometric findings correlate significantly with anal sphincter defects visualized by TAUS. TAUS is useful in the evaluation and management of patients with fecal incontinence.

Adult↗
PubMed1993

Laparoscopic colectomy: a critical appraisal.

A multicenter retrospective study was undertaken to assess the efficacy and safety of laparoscopy in colon and rectal surgery. To minimize potential bias in interpretation of the results, all data were registered with an independent observer, who did not participate in any of the surgical procedures. Sixty-six patients underwent a laparoscopic procedure. Operations performed included sigmoid colectomy (19), right hemicolectomy (15), low anterior resection (6), colectomy with ileal pouch-anal anastomosis (IPAA) (5), and abdominoperineal resection (APR) (3). The conversion rate from laparoscopic colectomy to celiotomy was 41 percent. Major morbidity and mortality were 24 percent and 0 percent, respectively. Length of stay, hospital costs, and lymph node harvest were compared between the sigmoid resection and right hemicolectomy subgroups. Data from traditional sigmoid colectomies and right hemicolectomies were obtained from the same institutions for comparison. Mean postoperative stay for laparoscopically completed sigmoid and right colectomies was significantly less than that for either the converted or the traditional groups (P < 0.02). Total hospital cost for traditional right hemicolectomy was significantly less than that for the converted group (P < 0.05) but not the laparoscopic group. Laparoscopic sigmoid resection showed no significant total hospital cost difference among traditional, converted, and laparoscopic groups. Lymph node harvest in resections for carcinoma was comparable in all groups. These preliminary data suggest that laparoscopic colon and rectal surgery can be accomplished with acceptable morbidity and mortality when performed by trained surgeons. Length of stay is shorter, but there is no proven total hospital cost benefit. Appropriate registries will be necessary to adequately assess long-term outcome.

Adolescent↗
PubMed1993

Transrectal ultrasound of rectal tumors.

Since preoperative staging of rectal tumors is important in planning treatment, we evaluated transrectal ultrasound (TRUS) staging of rectal neoplasms. In 35 consecutive rectal tumors, we compared TRUS staging results with final pathologic staging. TRUS predicted the degree of tumor invasion in 19 of 24 patients (79%) and the presence or absence of lymph node metastasis in 11 of 15 patients (73%). TRUS overestimated the degree of tumor invasion in four patients (17%) and underestimated invasion in one patient (4%). The depth of tumor invasion was correctly predicted in all 14 tumors located within 6 cm from the anal verge, but, beyond 6 cm, only 5 of 10 tumors (50%) were staged correctly (p = 0.005). In the group of 11 patients who underwent preoperative radiotherapy, pretreatment TRUS predicted the depth of tumor invasion in only six patients (55%) and overestimated tumor invasion in five patients (45%), suggesting that nearly half of these tumors were downstaged by radiotherapy. TRUS accurately predicts the degree of tumor invasion, especially in tumors closer to the anal verge, allowing for better treatment planning in patients with low to middle rectal neoplasms.

Adult↗
PubMed1993

Pre-operative staging of colorectal carcinoma using positron emission tomography.

Positron emission tomography (PET) is a unique technique for imaging functional metabolism of normal and diseased tissue. Accelerated rate of glucose metabolism typical of malignant tumor cells can be detected by using fluorine-18 deoxyglucose. In this pilot study, PET FDG imaging was compared to computerized tomography for the pre-operative staging of colorectal carcinoma. We prospectively evaluated 16 patients by simultaneously performing PET FDG and CT imaging for lesions in the liver, colon and rectum. The results were compared to the operative findings in all patients. Twenty tumor sites (lymph nodes 5, colon and rectum 13, liver 2) were found on histology in 16 patients. On comparison with histology, sensitivity, specificity and predictive accuracy for detection of tumor sites were 90%, 66% and 87% with PET as compared to 60%, 100%, and 65% with CT. These findings represent increased sensitivity and predictive accuracy for staging of colorectal carcinoma with PET FDG imaging as compared to CT scanning.

Aged↗
PubMed1991

Selective localization of polyribosomes beneath developing synapses: a quantitative analysis of the relationships between polyribosomes and developing synapses in the hippocampus and dentate gyrus.

Previous studies have revealed that polyribosomes are selectively localized beneath post-synaptic sites on central nervous system (CNS) neurons, and are particularly prominent during periods of synapse growth. The present study evaluates whether polyribosomes are most prominent at a consistent time in the developmental history of the synapse, or instead at a consistent time in the life of the organism regardless of the state of synaptic maturation (suggesting a globally acting factor). We compare the time course of synaptogenesis and the association between polyribosomes and developing synapses in three regions that develop at different rates: the external and internal blades of the dentate gyrus, and the CA1 region of the hippocampus proper. Each region was examined electron microscopically at 1, 4, 7, 10, 15, 20, 28 and over 120 days of age, evaluating: (1) synapse density (the number of synaptic profiles/area of neuropil), (2) the width of the neuropil layers, (3) the proportion of synapses with underlying polyribosomes, and (4) the number of polyribosome-containing synapses/area of neuropil. As anticipated on the basis of the differences in cytogenesis, the time course of synaptogenesis was different in the three regions. In the external blade of the dentate gyrus, synapse density increased in a nearly linear fashion between birth and 15 days of age, and then continued to increase at a somewhat slower rate until 28 days of age. Synapse development in the internal blade was delayed by several days in comparison to the external blade. In CA1, synapse density increased slowly between 1 and 7 days, and then at a rapid rate between 7 and 28 days of age. In all three regions, the proportion of synapses with underlying polyribosomes was highest between 1 and 7 days of age, and then decreased as synapse density increased. However, the peak in the number of polyribosome-containing synapses/unit area of neuropil occurred at different times in the three regions (4-7 days of age in the external blade of the dentate gyrus and in CA1, and 20 days of age in the internal blade). In addition to further defining the relationship between polyribosomes and developing synapses, the present study provides a data base on the time course of synapse development in the hippocampus and dentate gyrus, which will be useful for comparisons with other measures.

Aging↗
PubMed1990

Linkage of an autosomal dominant clefting syndrome (Van der Woude) to loci on chromosome Iq.

Van der Woude syndrome (VWS) is an autosomal dominant disorder in which affected individuals have one or more of the following manifestations: cleft lip, cleft palate, hypodontia, or paramedian lower-lip pits. VWS is a well-characterized example of a single-gene abnormality that disturbs normal craniofacial morphogenesis. As a first step in identifying genes involved in human development, we used a candidate-gene-and-region approach to look for a linkage to VWS. Six families with 3 or more generations of affected individuals were studied. Evidence for linkage (theta = 0.02, lod score = 9.09) was found between the renin (REN) gene on 1q and VWS. Other linked loci included CR1, D1S58, and D1S53. The genes for laminin B2 (LAMB2), a basement-membrane protein, and for decay-accelerating factor (DAF) were studied as possible candidate genes on 1q. Recombinants between VWS and both LAMB2 and DAF excluded these genes from a causal role in the etiology of VWS for the families studied in this report. Multipoint linkage analysis indicated that the VWS locus was flanked by REN and D1S65 at a lod score of 10.83. This tight linkage with renin and other nearby loci provides a first step in identifying the molecular abnormality underlying this disturbance of human development.

Chromosomes, Human, Pair 1↗
PubMed1986

Protein-synthetic machinery at postsynaptic sites during synaptogenesis: a quantitative study of the association between polyribosomes and developing synapses.

Previous studies have revealed dramatic accumulations of polyribosomes under growing spine synapses, suggesting a critical role for protein synthesis at the postsynaptic site during synaptogenesis. The present study quantitatively analyzes the distribution of polyribosomes under synapses during developmental synaptogenesis in the rat's dentate gyrus. The middle molecular layer of the suprapyramidal blade of the dentate gyrus was examined electron-microscopically at 1, 4, 7, 10, 15, 20, and 28 d of age. At each age, we evaluated (1) synapse density (the number of synapses/100 micron2 of neuropil), (2) the width of the molecular layer, (3) the proportion of spine synapses with underlying polyribosomes, and (4) the number of polyribosome-containing synapses/1000 micron2 of neuropil. From the first two measures, an estimate was obtained of the total extent of synaptogenesis, taking into account both the increase in synapse density and the increase in total area of neuropil. At 1 d of age, very few synapses were found in the molecular layer of the dentate gyrus, and those that were present were quite immature in appearance. Synapse density increased about 140-fold between 1 and 28 d of age, from an average of 0.36 synapses/100 micron2 at 1 d of age to 49 synapses/100 micron2 at 28 d of age. An inverse relationship was found between synapse density and the proportion of synapses with polyribosomes. Between 1 and 7 d of age, about 60% of the spine synapses had one or more polyribosomes under the spine base. Thereafter, the proportion of spines with polyribosomes decreased as synapse density increased. Similarly, the proportion of shaft synapses with underlying polyribosomes was greatest between 1 and 7 d postnatal, and decreased thereafter. While the proportion of synapses with polyribosomes was greatest between 1 and 7 d, the actual number of polyribosome-containing synapses/1000 micron2 of neuropil was negligible at 1 d, increased to a peak at 7 d of age, and then decreased as synapse density increased. Qualitatively, the most dramatic accumulations of polyribosomes were also found at 7 d of age. We conclude that spine-associated polyribosomes represent a structural specialization of dendrites at sites of synapse construction and as such may represent a marker for growing synapses. We propose that these elements produce protein(s) that are critically involved in the formation of the synaptic contact.

Animals↗
PubMed1985

Polyribosomes under developing spine synapses: growth specializations of dendrites at sites of synaptogenesis.

We have previously reported that there is a dramatic increase in polyribosomes associated with dendritic spines during periods of synapse growth induced by denervating lesions. We suggested that polyribosomes at the postsynaptic site may somehow be involved in the growth of synapses. To evaluate this hypothesis further, the present study determines whether synapses which are growing in the developmental period also have accumulations of polyribosomes. We examined the dentate gyrus of the developing rat electron microscopically at 7, 10, 15, 20, and 28 days of age, which spans the major period of synaptogenesis in this structure. Qualitative observations revealed dramatic accumulations of polyribosomes under spine synapses in the youngest animals (7 and 10 days of age). With synapse development, the accumulations of polyribosomes became less dramatic, so that by 28 days of age, the neuropil of the dentate gyrus appeared qualitatively mature. To determine the relationship between polyribosomes under spine synapses and synapse development, quantitative electron microscopic methods were use to evaluate synapse density (number of synapses/100 micron 2), and the incidence of polyribosome-containing spines (proportion of spine synapses with underlying polyribosomes) in the neuropil of the dorsal blade of the dentate gyrus at each age. An inverse relationship was found between synapse density and the proportion of spines with polyribosomes. Synapse density increased in an almost linear fashion between 7 and 28 days of age to levels which were actually somewhat higher than in mature rats, whereas the incidence of polyribosome-containing spines was highest at the youngest ages and decreased with development. Thus, polyribosomes were most prominent under spine synapses during the period of maximal synapse growth. These results, together with our previous observations of increased numbers of polyribosomes under spines during lesion-induced growth, suggest that the polyribosomes represent a structural specialization of dendrites at sites of synapse construction. We propose that they produce protein(s) that are involved in synapse growth.

Animals↗