Protein requirements for Blue-fronted Amazon (Amazona aestiva) growth.

The objective of this study was to evaluate the protein requirements for hand-rearing Blue-fronted Amazon parrots (Amazona aestiva). Forty hatchlings were fed semi-purified diets containing one of four (as-fed basis) protein levels: 13%, 18%, 23% and 28%. The experiment was carried out in a randomized block design with the initial weight of the nestling as the blocking factor and 10 parrots per protein level. Regression analysis was used to determine relationships between protein level and biometric measurements. The data indicated that 13% crude protein supported nestling growth with 18% being the minimum tested level required for maximum development. The optimal protein concentration for maximum weight gain was 24.4% (p = 0.08; r(2) = 0.25), tail length 23.7% (p = 0.09; r(2) = 0.19), wing length 23.0% (p = 0.07; r(2) = 0.17), tarsus length 21.3% (p = 0.06; r(2) = 0.10) and tarsus width 21.4% (p = 0.07; r(2) = 0.09). Tarsus measurements were larger in males (p < 0.05), indicating that sex must be considered when studying developing psittacines. These results were obtained using a highly digestible protein and a diet with moderate metabolizable energy levels.

Bacteroides fragilis enterotoxin induces the expression of IL-8 and transforming growth factor-beta (TGF-beta) by human colonic epithelial cells.

Bacteroides fragilis toxin (BFT) has been shown to be capable of inducing intestinal mucosal inflammation in animals. Such inflammation may be responsible for diarrhoea, which occurs in some, but not all human carriers of enterotoxigenic strains of B. fragilis (ETBF). We have studied responses to BFT by different human intestinal epithelial cell lines and subsequently investigated the expression of IL-8 and TGF-beta by T84 cells. The latter were selected because their responses to BFT, characterized by morphological changes and cell death by apoptosis, were similar to those we have recently observed in primary human colonocytes. We show that BFT dose-dependently increased the expression of transcripts and protein of the polymorphonuclear cell chemoattractant IL-8. BFT also dose-dependently induced the release of TGF-beta, which has been shown to enhance the repair of the injured intestinal epithelium. However, the secreted TGF-beta was almost exclusively in the biologically inactive form, as determined by Mv1Lu bioassay. Our studies therefore suggest that exposure of colonic epithelial cells in vivo to high concentrations of BFT can initiate an inflammatory response via secreted IL-8. BFT-induced release of latent TGF-beta may facilitate the subsequent repair of the injured epithelium, following its activation by proteases from neighbouring cells. Variation in cytokine responses by colonic epithelial cells in vivo could be an important determinant in the development of mucosal disease and symptoms in response to ETBF.

Heterogeneity in responses by primary adult human colonic epithelial cells to purified enterotoxin of Bacteroides fragilis.

BACKGROUND: Enterotoxigenic strains of Bacteroides fragilis (ETBF) have been implicated in diarrhoeal illness in livestock and children, but their role in adult human colonic disease is unknown. AIMS: To investigate responses by primary adult human colonic epithelial cells to purified B fragilis toxin (BFT). METHODS: BFT was purified from culture supernatant of a highly toxigenic strain of ETBF. Morphological changes to primary colonic epithelial cells, in response to purified BFT, were studied in organ culture of colonic biopsy specimens from 15 adults. RESULTS: BFT induced epithelial cell cytotoxicity in colonic biopsy specimens from 12/15 subjects. The BFT induced morphological changes were characterised by epithelial cell rounding, separation from adjacent cells, and detachment from the basement membrane. In severely affected specimens, almost all the epithelial cells were affected. There was heterogeneity between subjects in the rate at which BFT induced epithelial cell cytotoxicity occurred. Furthermore, in colonic biopsy specimens from three subjects, exposure to BFT did not induce any significant morphological changes to epithelial cells. CONCLUSION: BFT is capable of inducing cytotoxicity in primary adult human colonic epithelial cells. Such an effect of ETBF derived BFT on epithelial cells in the colon in vivo would be expected to lead to mucosal inflammation and diarrhoea. Heterogeneity in responses by primary colonocytes probably reflects the outcome of host-BFT interactions. Such interactions in vivo could determine the occurrence of colonic disease in some individuals but not others.

Effect of Clostridium difficile toxin A on human colonic lamina propria cells: early loss of macrophages followed by T-cell apoptosis.

We have previously shown that Clostridium difficile toxin A induces detachment of human colonic epithelial cells from the basement membrane and subsequent cell death by apoptosis. Because these cells require adhesion-dependent signalling from the extracellular matrix for survival, their detachment from the basement membrane by other means also induces apoptosis. The role of toxin A in the induction of apoptosis therefore remains to be determined. In addition, sensitivities to C. difficile toxin A of lamina propria lymphocytes, macrophages, and eosinophils, which lie below the surface epithelium, are not known. In contrast to epithelial cells, these lamina propria cells do not require adhesion-dependent signalling from the extracellular matrix for survival, and this may allow the mechanisms of toxin A-induced cell death to be further investigated. The aim of this study was to investigate the effect of purified C. difficile toxin A on human colonic lamina propria T cells, macrophages, and eosinophils. We show that C. difficile toxin A induces loss of viability in isolated colonic lamina propria cell preparations containing the three different cell types in a dose- and time-dependent fashion. Exposure to high concentrations of the toxin led to loss of macrophages within 72 h. T-lymphocyte and eosinophil cell death was prominent at later time points and occurred by apoptosis. Exposure to toxin A also induced the production of tumor necrosis factor alpha by the isolated colonic lamina propria cells. However, the presence of neutralizing antibodies to this cytokine did not influence C. difficile toxin A-induced T-cell apoptosis. Moreover, purified T cells also underwent apoptosis following exposure to toxin A, implying that apoptosis occurred as a consequence of a direct interaction between T cells and the toxin. Our studies suggest that C. difficile toxin A is capable of suppressing human colonic mucosal immune responses by inducing early loss of macrophages followed by T-cell apoptosis.

Detection of enterotoxigenic Bacteroides fragilis and its toxin in stool samples from adults and children in Italy.

Stool samples from children and adults with and without diarrhea were examined for the presence of enterotoxigenic Bacteroides fragilis (ETBF) and its enterotoxin. A cytotoxic assay with HT-29 cells followed by neutralization with a hyperimmune antiserum were used to detect B. fragilis enterotoxin. ETBF isolates were recovered from 12% of healthy children and 17% of children with diarrhea (P = .42) and from 15% of healthy adults and 9.4% of adults with diarrhea (P = .31). Fecal B. fragilis enterotoxin was detected in four children (two with diarrhea and two without diarrhea) and in four adults with diarrhea. This study shows that in Italy, the rate of ETBF carriage is high, regardless if diarrhea is present. In some instances, the presence of ETBF is associated with detectable levels of fecal enterotoxin, but the significance of this finding deserves further evaluation.

Extracorporeal whole body hyperthermia treatment of HIV patients, a feasibility study.

The literature supports that the retrovirus, Human Immunodeficiency Virus (HIV), which is thought to cause Acquired Immunodeficiency Syndrome (AIDS), is heat sensitive at temperatures which can be achieved in man. Invasive or non-invasive induction of whole body hyperthermia (WBH) has been used to treat an array of illnesses, primarily in the field of oncology, until recently. Non-invasive methods have proven to be less toxic than invasive means. However, new technology and refined patient management have shown a dramatic decrease in the side effects with extracorporeal whole body hyperthermia (EWBH). The Food and Drug Administration granted a prospective trial for six HIV positive/AIDS patients to undergo a single treatment of EWBH, with patients randomized to a core temperature of either 41 or 42 degrees C. All patients had failed antiretrovirals and experienced at least one episode of an opportunistic infection. Organetics, Ltd., PS-1 extracorporeal, centrifugal pump device was used to induce EWBH. Results of this feasibility study demonstrated the ability of this equipment and technique to induce EWBH with acceptable toxicity. It was not possible to assess efficacy in this small study.

Bolus mitomycin C and 5-FU with sequential radiation for poor-prognosis locally advanced cervical cancer.

Forty patients with locally advanced cervical carcinoma were entered into a protocol utilizing the bolus administration of both mitomycin C (10 or 15 mg) on Day 1 and 5-fluorouracil (400 mg) on Day 1-5 followed by sequential pelvic irradiation on Day 6 between September 1980 and October 1985. All patients had poor-prognosis FIGO stage IB, IIB, IIIB, or IVA disease. Only patients with poor prognosis factors such as bulky tumor masses of 5 cm or greater noted on the initial physical exam (37 patients) or poorly differentiated histology (3 patients) were eligible for this study. There were three severe side effects seen in the 24 patients receiving 15 mg mitomycin C. One patient developed thrombocytopenia, one patient developed acute radiation enteritis, and the third patient developed radiation proctitis requiring laser therapy. Only 1 of 16 patients receiving 10 mg mitomycin C developed a complication (thrombocytopenia). Neutropenia was mild in all patients. No infections were seen. Thrombocytopenia never warranted platelet transfusion. No patients developed therapy-related bowel obstruction or fistulae. Median follow-up was 11.3 years with a range of 6.2-14.2 years. A complete response rate of 63%, a local control rate of 58%, and a 5-year survival rate of 44% were obtained. This does not appear to offer any benefit over radiation alone. This present study supports the superiority of higher dose concurrent infusional chemotherapy and radiation over low-dose sequential bolus chemotherapy and radiation.

Risk of cutaneous malignant melanoma in patients with 'classic' atypical-mole syndrome. A case-control study.

BACKGROUND AND DESIGN: There is an increased risk of developing cutaneous malignant melanomas (MMs) in patients with classic atypical-mole syndrome (AMS). This study compares the incidence of newly diagnosed MMs in patients with classic AMS (cases) with the incidence of newly diagnosed MMs developing in a population without classic AMS (control patients). The charts of 287 white patients with AMS and 831 white patients without AMS were reviewed for the occurrence of newly diagnosed invasive MMs during follow-up. Both cases and control patients were followed up regularly by total-body cutaneous examinations. The cumulative 10-year risk for developing newly diagnosed invasive MMs was calculated (life-table method) for each cohort. RESULTS: Of the 287 AMS cases, 10 developed a newly diagnosed invasive MM, resulting in a 10-year cumulative risk of 10.7%. Of the 831 control patients, two developed a newly diagnosed invasive MM, resulting in a 10-year cumulative risk of 0.62%. CONCLUSION: Patients with classic AMS, regardless of the presence of a personal and/or family history of MM, are at significantly increased risk of developing invasive MMs compared with control patients.

Stage II adenocarcinoma of the endometrium treated by two standard regimens of combined preoperative irradiation and surgery.

We retrospectively analyzed 77 patients with stage II endometrial carcinoma treated with standard regimens of preoperative radiotherapy (RT) and surgery (S). The age range was 31-74 years with a median of 56.3 years. Thirty-three patients received 40 Gy whole pelvis RT followed by either radical or modified radical hysterectomy. Forty-four patients received 50 Gy whole pelvis RT and sequential intrauterine and intravaginal cesium-137 brachytherapy followed by a simple hysterectomy. Median follow-up was 111 months. No patient was lost to follow-up. The overall 5-year actuarial survival was 78%. There was no significant difference between the two treatment groups. Several prognostic variables were analyzed. Those with histologic grade I and II had 5-year survival of 89% and 83%, respectively, compared to 62% for grade III (P =0.045). The 5-year survival for microscopic cervical involvement was 87% compared to 59% for gross involvement (P= 0.008). Patients with negative or microscopic residual tumor in the surgical specimen and those with negative lymph nodes had less risk of treatment failure. Local failure occurred in only 9%. Major complications (3%) were seen only in the radical surgery group. Combined preoperative RT and S provide high cure rates with minimal complications for patients with stage II endometrial carcinoma. Patients with adverse prognostic factors are candidates for trials of more aggressive local and systemic therapy.

Risk of another basal cell carcinoma developing after treatment of a basal cell carcinoma.

BACKGROUND: There is an increased risk of new basal cell carcinomas (BCCs) developing in a person who has had a BCC. OBJECTIVE: This study attempts to define the magnitude of this increased risk. METHODS: The charts of 260 white patients with a histologically proven BCC were reviewed for the occurrence of new BCCs. The cumulative 5-year incidence (modified life-table method) for new BCCs developing in these patients was compared with the 5-year incidence in the general white population of the United States. RESULTS: Of the 260 patients, new BCCs developed in 137 within an average of 38.3 months, a 5-year cumulative rate of one or more new BCCs of 45.2%. The yearly risk for new BCCs developing in the study population remained high during the 5-year interval. In the general white population of the United States, the maximal 5-year incidence was calculated to be 5% (p < 0.005, chi-square test). CONCLUSION: Patients with a history of BCC require life-long follow-up because of the high probability of new BCCs developing.

Electron beam therapy for skin cancer of the head and neck.

We retrospectively analyzed 99 patients with 115 sites of skin cancer, predominantly involving the head and neck, treated with electron beam therapy. Our objective was to determine the local control rate, radiotherapy reactions, cosmesis, and salvage treatment. Forty-three percent of patients received radiotherapy after biopsy, 41% were treated for recurrence following other modalities of treatment, and 16% had positive margins after surgical excision. With minimum and mean follow-up of 24 and 47 months, respectively, local control was achieved in 88% of patients. Six of 14 local recurrences were salvaged by surgery (five patients) and radiotherapy (one patient) for a total local control of 93%. Serial photographs and data were available to analyze cosmesis in 56 patients. Excellent or good cosmesis was achieved in 91%. Side effects were mild and self-limiting. EBT is highly efficacious and offers excellent cosmesis.

Results of surgery and radiotherapy for early breast cancer.

Primary radiotherapy for 127 early breast cancers produced five-year local control of 96.1 percent and NED results of 81.1 percent. Results from a large community cancer center in New Jersey are comparable to results of major university cancer centers.

Early stage pure seminoma testis.

Forty-three patients with early stage pure seminoma of the testis were analyzed retrospectively. All patients were treated with orchiectomy and radiation therapy. Overall survival was 97.7 percent, with followup ranging from 4.3 to 17.4 years.

Reconstructive breast surgery following mastectomy and adjunctive radiation therapy.

With modern radiation, surgical therapy, and surgical reconstructive techniques, it is now possible to give adequate treatment for breast cancer and to reconstruct the breast as well, using a silicone implant prosthesis. Twelve mastectomies and reconstructions were performed on 8 patients. Seven of these had pre- or postoperative irradiation to one breast region, and 1 patient received irradiation to both breast areas. The clinical staging of patients with combined irradiation and surgery was Stage I--3 cases; Stage II--4 cases; and Stage III--1 case. Primary surgical procedures consisted of modified radical mastectomy for ten breast lesions and simple mastectomy for two others. Megavoltage radiotherapy was administered with a CO-60 Unit. Pre-operative irradiation of 4000 rads to the breast, chest wall, and regional lymphatics was given to 3 patients. Postoperative radiation therapy of 5000 rads to the chest wall and 4400-5000 rads to the regional lymphatics was given to 5 other patients, one of whom received bilateral irradiation. Adjunctive chemotherapy was employed in 5 patients with interruption during the period of implant surgery. Reconstructive surgery was performed 5 months to 14 months after irradiation in 7 patients and 51/2 years later in one patient. The procedure was a single stage operation with placement of a silicone prosthesis under the pectoralis muscle. No significant morbidity was encountered from radiotherapy, chemotherapy, or from the surgical procedures. Healing of surgical wounds after implantation was uncomplicated. Cosmetic results have been good. All patients are alive and well, 8 months to 6 1/2 years postirradiation and three months to three years post-breast reconstruction. Results to date have been most gratifying.