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Biomedical subjects

R Birch

Publications and source records attributed to R Birch.

At least 73 records · Page 4Linked to original sources
PubMed1998

GDNF and its receptor component Ret in injured human nerves and dorsal root ganglia.

Glial cell line-derived neurotrophic factor (GDNF) is trophic to motor and sensory neurones in animal models. GDNF mRNA is up-regulated in Schwann cells after peripheral nerve injury in rats. We have quantified and localized GDNF and its receptor component Ret, for the first time in any species, in injured human peripheral nerves and dorsal root ganglia (DRG) avulsed from the spinal cord. Significantly higher levels of GDNF were found in nerve distal to the site of the injury than in proximal or intact nerve, and in avulsed DRG than in post-mortem control DRG. GDNF immunostaining was seen in Schwann cells and in DRG neurones, especially of small and medium size, with significantly increased numbers of medium sized sensory neurones immunoreactive for GDNF after avulsion. Ret immunoreactivity was restricted to DRG neurones and axons, with no significant changes in numbers of positive DRG cells after injury. Our findings suggest that GDNF may play a role in injured human nerves and sensory ganglia, particularly in medium sized sensory neurones.

Adolescent↗
PubMed1998

The use of facsimiles in acute patient transfers: experience with brachial plexus injuries.

In order to optimize the transfer of patients with acute brachial plexus injuries a facsimile proforma was introduced. The transfer of 20 patients prior to its introduction was compared as a retrospective control group with a prospective analysis of 20 patients transferred after the introduction of the facsimiles. There were many fewer missed injuries, the patients were better investigated and it as easier to decide when to delay patient transfer. Subjectively there was a considerably easier passage of both medical and social information about the patients. The cost of the facsimile and its use is more than compensated by the savings in reduced impatient stay, the reduced need for urgent tests upon receipt of the patient, fewer phone calls and considerably reduced administrative workload.

Brachial Plexus↗
PubMed1998

A morphological study of Schwann cells and axonal regeneration in chronically transected human peripheral nerves.

Relatively little is known about the effects of chronic transection on human peripheral nerves. In this study intraoperative biopsies were obtained from proximal and distal nerve stumps and intervening neuromas resected before peripheral nerve reconstruction. Biopsies were collected from ten patients following differing types of nerve injury, with delays to repair ranging from 8 to 53 months. Nerves were examined by light and electron microscopy. In general, reinnervation was poor, although even following the most severe injuries, all of the distal stumps contained some regrowing axons, which were always associated with Schwann cells. Denervated Schwann cells, arranged in typical bands of Büngner were consistently present in each distal stump. Our findings confirm that the morphology of chronically denervated human peripheral nerves is essentially similar to that described in experimental models.

Adolescent↗
PubMed1998

Pain following human brachial plexus injury with spinal cord root avulsion and the effect of surgery.

Brachial plexus injury leading to spinal cord root avulsion in humans produces a characteristic constant crushing and intermittent shooting pain, which is often intractable. Preliminary observations suggested that this pain might be alleviated after successful nerve transfers to restore limb function. We therefore studied a group of 14 patients prospectively, to establish the validity of this observation, and to elucidate the underlying mechanisms. We found a strong correlation and temporal relationship between reduction in pain and successful nerve repair. All five patients with motor recovery experienced significant relief of de-afferentation pain, while in the seven patients with persistent pain, none had motor recovery. There was no correlation between pain relief and the minimal recovery of sensation in some cases, and no case had any return of sensory or sympathetic cutaneous axon-reflexes. While skin sympathetic axon-reflexes were reduced with T1 root lesions, there was no relationship between T1 root damage and pain. It was concluded that nerve repair can reduce pain from spinal root avulsions and that the mechanism may involve successful regeneration, and/or restoration of peripheral connections prior to their function, possibly in muscle.

Analgesics↗
PubMed1998

A randomized trial of once vs twice daily administration of intravenous granisetron with dexamethosone in patients receiving high-dose cyclophosphamide, thiotepa and carboplatin.

The purpose of this study was to determine the optimal schedule of i.v. granisetron and dexamethosone for control of nausea and emesis in patients receiving high-dose chemotherapy (HDC). Seventy patients with breast cancer received high-dose cyclophosphamide, thiotepa and carboplatin (CTCb) for 3 consecutive days. All 70 received dexamethasone 12 mg i.v. and granisetron 1 mg i.v. prior to infusion of CTCb and were randomized to receive placebo (n = 37) or an additional identical dose of granisetron (n = 33) 12 h later. Beginning on day 2 of chemotherapy administration, 55 patients evaluable later self-administered a cocktail of diphenhydramine (benadryl), lorazepam (ativan) and dexamethasone (BAD). Fourteen of 37 patients (38%) receiving granisetron once a day and 15/33 (44%) receiving it twice a day had a complete response during the first 24 h following the first doses of chemotherapy (P = 0.52). In the 55 evaluable patients receiving BAD, 18 of 29 (62%) in the once daily group and 14/26 (54%) in the twice daily group required additional medications (P = 0.54). The median time to first emetic episode was 20 h (range 6.6-79.5) for patients receiving once a day and 21.4 hours (range 5.8-105.3) for patients receiving twice a day granisetron (P = 0.48). Five patients in the once daily and seven patients in the twice daily group had complete control of nausea and emesis throughout the study period (P = 0.37). It was concluded that there were no statistically significant differences in nausea and emetic control between dexamethasone with once daily or twice daily i.v. granisetron administration in patients receiving high-dose CTCb.

Adult↗
PubMed1998

Mobilization and harvesting of peripheral blood stem cells: randomized evaluations of different doses of filgrastim.

The effects of different doses of filgrastim on yields of CD34+ peripheral blood stem cells were evaluated in patients with breast cancer. 55 were randomized to receive filgrastim 10, 20, 30 or 40 microg/kg/d with more CD34+ cells/kg/apheresis harvested after the three highest dose levels. 35 additional patients were randomized to receive 10 or 30 microg/ kg. The median number of CD34+ cells collected after 10 microg/ kg (n = 31) was 0.7 x 10(6)/kg/apheresis (range 0.1-4.4) as compared to 1.2 (range 0.1-6.8) after 30 microg/kg (n = 32) (P = 0.04). Among patients randomized to 10 v 30 microg/kg, more (50%) achieved > or = 5.0 x 10(6) CD34+ cells/kg and less aphereses were required to achieve > or = 2.5 x 10(6) CD34+ cells/kg after the higher dose (P = 0.04). In multivariate analyses, patients receiving 10 microg/kg (n = 31) had lower yields of CD34+ cells (P = 0.026) and had a 3.3-fold increase in the probability of not achieving > or = 5.0 x 10(6) CD34+ cells/kg as compared to patients receiving 20-40 microg/kg (n = 59). Patients who had received radiation had a 2.9-fold probability of not achieving > or = 2.5 x 10(6) CD34+ cells/kg. These data suggest that, in patients with good marrow reserves, doses of filgrastim > 10 microg/kg/d mobilized more CD34+ cells and may be useful when high numbers of CD34+ cells are desired.

Antigens, CD34↗
PubMed1998

A randomized trial of two doses of cyclophosphamide with etoposide and G-CSF for mobilization of peripheral blood stem cells in 318 patients with stage II-III breast cancer.

The purpose of this study was to develop a less toxic outpatient chemotherapy regimen for mobilizing peripheral blood stem cells (PBSC). Three hundred eighteen patients with newly diagnosed stage II-III breast cancer who had received conventional dose adjuvant chemotherapy were randomized to receive intermediate-dose cyclophosphamide (2 g/m2), etoposide (600 mg/m2), and granulocyte colony-stimulating factor (G-CSF) 6 micrograms/kg/day (ID-Cy, n = 162) or high-dose cyclophosphamide (4 g/m2) and the same doses of etoposide and G-CSF (HD-Cy, n = 156) followed by collection of PBSC. Three hundred seventeen of 318 patients had apheresis performed, and 315 received high-dose chemotherapy (HDC) followed by PBSC support. The median numbers of CD34+ cells collected in a median of two apheresis following ID-Cy and HD-Cy were 19.9 and 22.2 x 10(6)/kg, respectively (p = 0.04). The fractions of patients achieving CD34+ cell doses > or = 2.5 or > or = 5.0 x 10(6)/kg were not different between the two regimens. More patients receiving HD-Cy had grade 3-4 nausea (p = 0.001), vomiting (p = 0.03), and mucositis (p = 0.04). The fractions of patients having a neutrophil nadir < 0.5 x 10(9)/L following ID-Cy and HD-Cy were 0.83 and 0.95, respectively (p = < 0.001). The fractions of patients having a platelet nadir < 25 x 10(9)/L following ID-Cy and HD-Cy were 0.13 and 0.51, respectively (p = < 0.001). More patients in the HD-Cy group received platelet (p < 0.001) and red blood cell (p < 0.001) transfusions and were admitted to the hospital more frequently (p = 0.03) than patients receiving ID-Cy. Three hundred fifteen patients received HDC followed by infusion of PBSC. There were no significant differences in the incidence of transplant-related death or early survival between patients receiving ID-Cy or HD-Cy followed by HDC. It was concluded that a regimen of Cy 2 g/m2 with etoposide and G-CSF was effective for mobilization of PBSC with low morbidity and resource utilization in patients with limited prior chemotherapy exposure.

Adult↗
PubMed1998

Sequential treatment including high-dose chemotherapy with peripheral blood stem cell support in patients with high-risk stage II-III breast cancer: outpatient administration in community cancer centers.

The authors determined outcomes for patients with localized high-risk breast cancer undergoing sequential outpatient treatment with conventional-dose adjuvant therapy, chemotherapy, and growth factor mobilization of peripheral blood stem cells (PBSC) and high-dose chemotherapy (HDC) with PBSC support in community cancer centers. Ninety-six patients with stage II-IIIB noninflammatory breast cancer with 10 or more positive lymph nodes and a median age of 46 years (range, 22-60 years) were treated with: 1) doxorubicin, 5-fluorouracil, and methotrexate (AFM), four courses at 2-week intervals; 2) cyclophosphamide (4 g/m2) and etoposide (600 mg/m2) (CE), followed by filgrastim (6 microg/kg per day) and PBSC harvest; and 3) cyclophosphamide (6 g/m2), thiotepa (500 mg/m2), and carboplatin (800 mg/m2) (CTCb), followed by PBSC infusion. All 96 patients received AFM, 95 (99%) received CE, and 95 (99%) received CTCb with a median hospital stay of 12 days (5-34 days) for all phases of treatment. Sixty-nine patients (72%) are alive, 55 (57%) without relapse at a median follow-up of 53 months (range, 37-77 months). One patient (1%) died of acute myeloid leukemia and all other deaths were associated with recurrent breast cancer. The probabilities of event-free survival (EFS) at 4 years for patients with or without locally advanced disease were 0.37 and 0.69, respectively (p = 0.004), and 0.71 and 0.48 for patients who were estrogen/progesterone receptor (ER/PR) positive or ER/PR negative, respectively (p = 0.016). In multivariate analyses, locally advanced disease (relative risk, 2.3; p = 0.021) and ER/PR-negative hormone receptor status (relative risk, 2.2; p = 0.014) were the only adverse risk factors for EFS identified. Patients with zero, one, or two of these adverse risk factors had 4-year EFS of 0.80, 0.56, and 0.33, respectively. The sequential administration of AFM, CE, and CTCb followed by PBSC in an outpatient community setting was well tolerated in patients with high-risk stage II-III breast cancer. More intensive or more novel treatment strategies will be required to decrease relapses in patients who have ER/PR-negative tumors and/or have locally advanced disease.

Adult↗
PubMed1998

Knee pain and the infrapatellar branch of the saphenous nerve.

Pain over the front of the knee is common after surgery or trauma but often a definite diagnosis is difficult to make. Over the past year we have seen five cases in which the pain could be ascribed to damage to a branch of the infrapatellar branch of the saphenous nerve. Two were subsequent to trauma and three to surgical procedures. In all five cases surgical exploration gave symptomatic relief. Eight cadaveric knees were prosected to explore further the anatomy of this nerve in relation to the injuries. Injury to one of these branches should be considered in cases of persistent anterior, anteromedial or anterolateral knee pain or neurological symptoms following surgery or trauma.

Adult↗
PubMed1998

The Rationale for Performing Autologous Peripheral Blood Stem Cell Transplants in Community Cancer Centers.

There is debate over whether or not the technology of peripheral blood stem cell (PBSC) support of high-dose chemotherapy (HDC) should be disseminated to practicing oncologists or continue to be administered only in academic referral centers. High-dose therapy with stem cell support is now the standard of care for selected patients with lymphoma, multiple myeloma and possibly breast cancer. Such therapies, delivered in a clinical trials setting, need to be more widely available to eligible patients. This manuscript presents the rationale for performing HDC with PBSC support in community cancer centers. The availability of PBSC has made the delivery of well-established HDC regimens safe and effective in an outpatient setting. Delivery of such therapy where the patient lives has many economic and social advantages to the patient compared to referral to a transplant center. In addition, more patients can be treated more cost effectively if such therapy is administered locally where the patient lives. From the scientific point of view, improved access to HDC in the community should increase accrual to clinical trials, allowing the generation of outcome data more rapidly.

Journal Article↗
PubMed1997

Endogenous NGF and CNTF levels in human peripheral nerve injury.

Nerve growth factor (NGF) is trophic to sensory and sympathetic fibres, and ciliary neurotrophic factor (CNTF) to motoneurones, in animal models of peripheral nerve injury: NGF excess produces hyperalgesia. In this first study of injured human nerves and sensory ganglia, we quantified and localized endogenous NGF and CNTF in 59 neonate and adult patients with brachial plexus and peripheral nerve injury. NGF levels were generally depleted in injured nerves, but relatively preserved acutely in nerve segments distal to injury. NGF immunostaining was observed in Schwann cells in distal nerve segments with pockets of high levels in some neuromas. CNTF levels and immunostaining in Schwann cells were markedly decreased distally within days of injury. We propose that early local administration of NGF and CNTF-like agents may help prevent degenerative changes in injured nerves, while at later stages local anti-NGF treatment (e.g. of some neuromas) may ameliorate chronic pain.

Adolescent↗
PubMed1997

Mitoxantrone, 5-fluorouracil, and high dose leucovorin (NFL) versus intravenous cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) in first-line chemotherapy for patients with metastatic breast carcinoma: a randomized phase II trial.

BACKGROUND: Previous Phase II studies using the combination of mitoxantrone, 5-fluorouracil, and high dose leucovorin (NFL) in the treatment of metastatic breast carcinoma have shown this regimen to be active and well tolerated. In this randomized Phase II study, the authors compared the NFL regimen with a standard CMF regimen in the first-line therapy of patients with metastatic breast carcinoma. METHODS: One hundred twenty-eight women receiving their first chemotherapy for metastatic breast carcinoma were entered into this randomized study. Sixty-four patients were treated with NFL: mitoxantrone 12 mg/m2 IV on Day 1; leucovorin 300 mg IV over 30-60 minutes on Days 1, 2, and 3, immediately preceding administration of 5-fluorouracil; and 5-fluorouracil 350 mg/m2 IV bolus on Days 1, 2, and 3. Sixty-four patients received CMF: cyclophosphamide 600 mg/m2 IV on Day 1; methotrexate 40 mg/m2 IV on Day 1; and 5-fluorouracil 600 mg/m2 IV on Day 1. Both regimens were repeated at 21-day intervals; responding patients received at least 8 courses. RESULTS: Patients treated with NFL had a higher response rate than patients treated with the CMF regimen (45% vs. 26%, respectively; P = 0.021). Median duration of response was 9 months with NFL and 6 months with CMF (P = 0.10); 11 patients had long responses (>12 months) with NFL versus 4 patients with CMF (P = 0.06). Median survival was similar for both groups. Both regimens were well tolerated, with infrequent Grade 3 or 4 toxicities. CONCLUSIONS: NFL is an active, well-tolerated regimen for the treatment of metastatic breast carcinoma; it produced a higher response rate than the CMF regimen used in this study. Although more intense CMF regimens or regimens containing doxorubicin would likely increase the response rate, they would almost certainly do so with the consequence of greater toxicity as compared with NFL. NFL is an excellent initial palliative treatment option for elderly patients or patients who have exhibited poor tolerance for other chemotherapy regimens.

Adult↗
PubMed1997

Induction, mobilization of peripheral blood stem cells (PBSC), high-dose chemotherapy and PBSC infusion in patients with untreated stage IV breast cancer: outcomes by intent to treat analyses.

We investigated the outcomes of patients with breast cancer undergoing induction chemotherapy, mobilization of peripheral blood stem cells (PBSC) and high-dose chemotherapy (HDC) with PBSC infusion. One hundred and fourteen patients with untreated stage IV breast cancer, with a median age of 46 years (range 24-62), were entered on a phase II trial consisting of; (1) doxorubicin, 5-flurouracil, methotrexate (AFM) x 4 courses at 2 week intervals; (2) cyclophosphamide (4 g/m2), etoposide (600 mg/m2), cisplatin (105 mg/m2) (CEP), filgrastim (6 micrograms/kg/day) and PBSC collection; (3) cyclophosphamide (6 g/m2), thiotepa (500 mg/m2), carboplatin (800 mg/m2), (CTCb) followed by PBSC infusion. All patients received AFM, 107 (94%) received CEP, 93 (82%) received CTCb and PBSC as per protocol and 99 (87%) ultimately received HDC and PBSC. There was one infectious death after AFM and all other deaths were associated with progressive disease. Fifty-two patients (46%) are alive, 21 (18%) without progression, at a median 31 months (range 22-47). The probabilities of survival and progression-free survival at 3.5 years were 0.40 and 0.17, respectively. All 62 patients with visceral disease and/or a prior history of doxorubicin adjuvant therapy have relapsed or progressed. We conclude that the sequential administration of AFM, CEP and CTCb followed by PBSC resulted in long-term PFS only in patients who were NED, had bone-only disease or had lymph node or soft tissue disease with or without bone disease. Other strategies, aimed at improving responses to initial therapy, improving HDC regimens and/or developing immunomodulatory therapies, will be necessary to improve PFS for patients who fail doxorubicin adjuvant or who have visceral disease.

Adult↗
PubMed1997

Collection of peripheral blood progenitor cells after the administration of cyclophosphamide, etoposide, and granulocyte-colony-stimulating factor: an analysis of 497 patients.

BACKGROUND: There is great interpatient variability in the number of peripheral blood stem cells collected, as measured by CD34+ cell content, after the administration of chemotherapy and a growth factor. The ability to predict patients who fail to yield adequate quantities of CD34+ cells would be of value. However, very few reports include large numbers of patients treated in an identical fashion. STUDY DESIGN AND METHODS: Between 1991 and 1995, 497 consecutive patients with a variety of malignant diseases received cyclophosphamide (4 g/m2), etoposide (600 mg/m2), and granulocyte-colony-stimulating factor (6 micrograms/kg/day) for mobilization and collection of a target dose > or = 2.5 x 10(8) CD34+ cells per kg. Multivariate analyses were performed to determine the factors associated with failure to achieve this target harvest. RESULTS: A median of 14.71 x 10(6) CD34+ cells per kg (range, 0.08-137.55) was harvested with a median of 2 (range, 1-11) apheresis procedures. Ninety-one percent of patients yielded > or = 2.5 x 10(5) CD34+ cells per kg. Patients with Stage II-III breast cancer, who had pretreatment platelet counts > or = 150 x 10(9) per L and patients who underwent < or = 1 prior chemotherapy regimen had improved CD34+ cell yields. However, most patients with adverse risk factors yielded > or = 2.5 x 10(6) CD34+ cells per kg. CONCLUSION: A regimen of cyclophosphamide, etoposide, and granulocyte-colony-stimulating factor led to the successful collection of adequate numbers of CD34+ cells in most patients without excessive toxicity. These observations confirm previous reports that intense prior therapy adversely affects the quantity of CD34+ cells harvested. Pretreatment and posttreatment variables did not predict with any certainty the small fraction of patients who fail to yield > or = 2.5 x 10(6) CD34+ cells per kg via multiple apheresis procedures.

Adolescent↗
PubMed1997

Collection of peripheral blood stem cells following administration of paclitaxel, cyclophosphamide, and filgrastim in patients with breast and ovarian cancer.

PURPOSE: To determine the toxicities and efficacy of paclitaxel, cyclophosphamide (Cy), and recombinant human granulocyte-colony stimulating factor (filgrastim) administered for mobilization and collection of peripheral blood stem cells (PBSC) in patients with breast and ovarian cancer. METHODS: One hundred and forty-one patients with breast (n = 115) or ovarian cancer (n = 26) received paclitaxel 170 mg/m2 and Cy 2 gm/m2 (n = 42) or paclitaxel 200 mg/m2, Cy 3 gm/m2 (n = 99), and filgrastim (6 micrograms/kg/day) followed by collection of PBSC by apheresis. RESULTS: The 2 dose levels of paclitaxel and Cy tested were well tolerated. The median yield of CD34+ cells from all patients was 6.53 x 10(6)/kg (range, 0.11-51.76) collected with a median of 2 aphereses (range, 1-8). The target dose of 2.5 x 10(6) CD34+ cells/kg was achieved in 85% of patients. The mean daily collection of CD34+ cells was 5.46 x 10(6)/kg for patients receiving 200 mg/m2 of paclitaxel and 3 gm/m2 of Cy as compared to 2.77 for patients receiving the lower doses (p = 0.0005). Increasing the dose of paclitaxel and Cy did not significantly increase the fraction of patients achieving a target dose of 2.5 x 10(6) CD34+ cells/kg (87% vs 81%, p = 0.367) but did increase the fraction achieving a target of 5.0 x 10(6) CD34+ cells/kg (73% vs 45%, p = 0.002). The mean daily collection of CD34+ cells for patients who had received only 1 prior chemotherapy regimen was 6.59 x 10(6)/kg as compared to 3.47 for patients who had received more than 1 prior chemotherapy regimen (p < 0.0001). Prior radiation therapy (p = 0.003) and patient performance status (p = 0.047) were adverse risk factors for achieving a target dose of > or = 2.5 x 10(6) CD34+ cells/kg. CONCLUSIONS: The combination of paclitaxel, Cy, and filgrastim can be administered with acceptable toxicity, allowing collection of adequate quantities of PBSC from the majority of patients with breast and ovarian cancer. Increasing the doses of paclitaxel and Cy increased the number of CD34+ cells collected and decreased the number of apheresis procedures necessary to collect target cell doses. However, increasing drug doses did not increase the fraction of patients yielding the minimum CD34+ target dose of 2.5 x 10(6)/kg. Collection of PBSC early in the disease course is the best strategy to assure optimal CD34+ cell doses in all patients.

Adult↗
PubMed1997

A randomized study of etoposide and carboplatin with or without paclitaxel in the treatment of small cell lung cancer.

Small cell lung cancer accounts for 20% to 25% of all lung cancer cases and is initially responsive to combination chemotherapy. However, the majority of patients relapse, and at that point their disease is highly resistant to chemotherapy. The combination of etoposide with either cisplatin or carboplatin is regarded as the standard of care for these patients. Previous studies have documented the activity of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) at doses of 135 to 250 mg/m2 administered over 1, 3, or 24 hours as either a single agent or in combination with etoposide and a platinum compound. Studies adding paclitaxel to etoposide/carboplatin (EP) have demonstrated complete responses in both limited and extensive disease, but all have been in single-arm phase II studies. Preliminary data also suggest the possibility of a dose-response curve for the combination. We recently began a randomized phase II/III comparison of the standard EP to EP plus paclitaxel for newly diagnosed patients with limited or extensive small cell lung cancer. Carboplatin in this study is dosed according to area under the concentration-time curve as calculated by the Calvert formula. The study compares EP (carboplatin area under the concentration-time curve of 6 intravenously [IV] over 30 to 60 minutes on day 1, with etoposide 120 mg/m2 IV days 1 to 3) versus EP plus paclitaxel (paclitaxel 200 mg/m2 IV 1-hour infusion on day 1, carboplatin area under the concentration-time curve of 6 IV over 30 to 60 minutes on day 1, and etoposide 50/100 mg orally on alternating days 1 to 10). The design, inclusion criteria, and staging of patients in this study will be presented with initial accrual and patient characteristics. Randomized studies of this type are essential if the true role of this new combination is to be fully evaluated.

Adult↗