Search PubMed⌕ Search

Biomedical subjects

J R Clark

Publications and source records attributed to J R Clark.

At least 73 records · Page 4Linked to original sources

T-cell subsets and natural killer cell function with squamous cell carcinoma of the head and neck.

Twenty-two patients with squamous cell carcinoma of the head and neck were studied to assess potential abnormalities in total T lymphocytes, T4/T8 ratios, and natural killer cell function. Total T-cell counts were reduced for the entire group with the greatest reduction occurring in individuals with hypopharyngeal tumors and/or stage IV disease. Helper to suppressor ratios were within the norm for the total group, but specific site variances were detected in patients with oral cavity and hypopharyngeal primary carcinomas. Similarly altered T4/T8 ratios were noted with stage III disease. Substantive differences in natural killer cell activity were not observed. These data suggest that perturbations in T-lymphocyte subsets can be associated with decreased survival.

Adult↗

Vascularity for healing of meniscus repairs.

Vascularity in the human meniscus is poor beyond 1-2 mm from the meniscosynovial junction, yet 22% of the tears in this series occur with a greater than or equal to 3-mm peripheral white rim. It is possible to suture these tears with the wider peripheral white rims, but healing rates are reduced because it is more difficult to obtain a satisfactory vascular supply. This article describes the history of our efforts at obtaining blood supply for healing of meniscus tears with a peripheral white rim up to 5 mm. Resection of the peripheral white rim to the vascular bed was unsatisfactory because it reduced the size of the meniscus and, by 3 years, the subsequent degenerative changes in the knee were comparable to meniscectomy. Holes made in the rim with a biopsy needle were again unsuccessful at improving healing. The present technique involves using rasps to abrade the parameniscal synovium on both the superior and inferior surface of the peripheral white rim. None of the peripheral white rim is resected. In the first series of 240 patients in whom peripheral white rim resection or the biopsy punch was used, the failure rate of meniscus healing was 22%. In a subsequent series of 68 patients (52 males, 16 females) who had 81 meniscal repairs by means of the rasp for parameniscal synovial abrasion, the failure rate was 9%. The rasp appears to be the safest and most effective method to gain vascularity for healing of meniscus repairs. It is possible to obtain healing with 5-mm peripheral white rims without resection of any portion of this rim, thus maintaining the full size of the meniscus.

Adolescent↗

An analysis of induction and adjuvant chemotherapy in the multidisciplinary treatment of squamous-cell carcinoma of the head and neck.

This study examines the role of combination chemotherapy with surgery and/or radiotherapy in the initial treatment of patients with advanced stage III and IV squamous-cell carcinoma of the head and neck (SCCHN). Two courses of initial (induction) cisplatin, bleomycin, and methotrexate with oral calcium leucovorin (PBM) were used with the principal intent of increasing the effectiveness of subsequent surgery and/or radiotherapy. Following induction chemotherapy and local treatment, disease-free patients who had responded to initial chemotherapy were entered into a randomized trial of adjuvant PBM. The response rates to induction PBM chemotherapy were a complete response (CR) rate of 26% and a partial response (PR) rate of 52%, for an overall response rate of 78%. A response to induction PBM was highly correlated with failure-free survival (P less than .0001). A Cox multistep regression analysis of potential prognostic factors was performed. After adjusting for the significant prognostic factors of performance status, initial tumor size, and primary tumor site, a response to induction chemotherapy remained independently associated with improved survival (P = .0002). The randomized trial of adjuvant chemotherapy demonstrated that such treatment significantly improved failure-free survival by decreasing local-regional failures. The benefit of adjuvant chemotherapy was particularly evident in patients who had a PR to induction chemotherapy (P = .01). The toxicity of this multidisciplinary approach was predictable and acceptable. Surgery and radiotherapy were not compromised by induction or adjuvant chemotherapy. Definitive evidence that chemotherapy can favorably influence survival awaits confirmation of these results by a randomized trial using a control arm of patients treated with conventional surgery and/or radiotherapy alone.

Aged↗

Induction chemotherapy as initial treatment for advanced head and neck cancer: a model for the multidisciplinary treatment of solid tumors.

The role of chemotherapy in the management of patients with SCCHN has not been adequately defined. For patients with recurrent or metastatic disease, several single agents can induce significant tumor regression in 20% to 40% of cases and provide palliation for the individual with a symptomatic or life-threatening lesion. However, complete or long-term control of tumor with chemotherapy alone remains poor. In addition, current regimens of combination chemotherapy have not proved superior to single agents in this setting. Thus, the routine use of combination chemotherapy for patients with metastatic or recurrent SCCHN cannot be justified outside an investigational study. New single agents of promise must be sought and more active combinations of chemotherapy devised for the treatment of patients with metastatic or recurrent SCCHN. Strategies for drug development include the investigation of cisplatin analogues, such as iproplatin and carboplatin, the exploitation of potentially synergistic drug schedules, and the administration of chemotherapy by continuous infusion. That the use of continuous-infusion drug delivery can enhance antitumor activity and limit toxicity for patients with recurrent or metastatic SCCHN was convincingly demonstrated by Kish and co-workers132 in a randomized trial of cisplatin with either bolus or continous-infusion 5-fluourouracil. The antitumor activity of combination chemotherapy may also be increased by the use of mid-cycle nonmyelosuppressive agents, such as methotrexate with leucovorin rescue, or the administration of alternating cycles of non-cross-resistant regimens of combination chemotherapy. The optimal use of chemotherapy in the multidisciplinary treatment of patients with previously untreated SCCHN must also be clarified. Uncontrolled studies of induction chemotherapy report increasingly positive results. Several regimens of induction combination chemotherapy are now associated with significant tumor regression in 70% to 90% of patients, and complete clinical regression of tumor in 20% to 50%. Of patients with a complete clinical response to induction chemotherapy, a complete pathologic response has been documented in 30% to 70% of patients who undergo surgical resection after chemotherapy. It is now evident that patients achieving a complete response to induction chemotherapy have a high probability of local-regional control of tumor and cure. Conversely, patients not responding to induction chemotherapy fare poorly regardless of subsequent local treatment, and it may be appropriate to defer excessively morbid surgical procedures in this patient populus.(ABSTRACT TRUNCATED AT 400 WORDS)

Antineoplastic Agents↗

Effects of aerial thermal fog applications of fenthion on caged pink shrimp, mysids and sheepshead minnows.

Mosquito control applications of fenthion by aerial thermal fog equipment were studied at 2 sites in Collier County, FL, for sprays that occurred on June 20 and 23, 1984. Acute, lethal effects of fenthion deposited in these estuarine habitats were assessed for caged pink shrimp (Penaeus duorarum), mysids (Mysidopsis bahia) and sheepshead minnows (Cyprinodon variegatus). At Site 1, along a bay with substantial dilution and tidal mixing, fenthion concentrations of 1.5 and 0.29 micrograms/liter were measured in samples taken immediately after both sprays. Concentrations decreased to less than or equal to 0.020 microgram/liter 12 h postspray and no mortality was observed for caged pink shrimp and mysids. Site 2 was along a residential canal system that offered limited dilution and mixing. Maximum concentrations were 2.6 and 0.51 micrograms/liter and measurable concentrations (greater than 0.038 microgram/liter) of fenthion persisted at this site for 4 days. Fenthion concentrations in surface waters were toxic to caged pink shrimp and mysids after both sprays. No mortality occurred among caged sheepshead minnows at either site.

Animals↗

Oral complications of multimodality therapy for advanced squamous cell carcinoma of head and neck.

Investigational treatment of advanced localized stage III or stage IV squamous cell carcinoma of the head and neck may include chemotherapy in addition to radiotherapy and surgery. Such therapy, while effective in eradicating local tumors, often produces considerable oral toxicity. In this study we reviewed the oral complications of 22 patients receiving multimodality cancer treatment. The addition of chemotherapy to the treatment regimen did not increase the incidence of complications (osteoradionecrosis, mucositis, xerostomia, radiation caries, or infection) when compared with historical controls receiving radiotherapy alone. Pretreatment dental evaluation and close follow-up of these patients are encouraged.

Carcinoma, Squamous Cell↗

Effects of parity, season, gonadotropin releasing hormone and altered suckling intensity on the interval to rebreeding in sows.

Two experiments were conducted to determine the effects of a) parity and season of the year on the interval from weaning to rebreeding in sows and b) altered suckling intensity (ASI) and gonadotropin releasing hormone (GnRH) on the postpartum interval in primiparous and multiparous sows. Experiment I included 406 weaning-to-rebreeding intervals in 172 primiparous and multiparous sows. Primiparous sows returning to estrus during the spring and summer months had a longer (P<0.001) rebreeding interval (11.0 d) than the other groups (5.7 d). In Experiment II, 32 sows were assigned to a factorially designed experiment. The factors were ASI, GnRH and parity. Treatments were begun 7 d before weaning (about 4 wk of age). The ASI was accomplished by separating the sow from her litter for 12 h each day. The average interval from the beginning of treatment to the onset of estrus was 13.4 d and was not affected (P>0.33) by ASI, GnRH, parity or their interactions. None of the factors was found to affect the average weaning weight of the piglets (P>0.05); however, piglets in the ASI group were heavier (P<0.03) at 1-wk postweaning than those in the no-ASI group. The results showed that primiparous sows returning to estrus during the spring and summer months had the longest rebreeding interval. Additionally, neither GnRH nor ASI, separately or in conjunction, decreased the postpartum interval in sows.

Journal Article↗

Time of onset of estrus in gilts.

An experiment was conducted to determine when, during a 24-h period, gilts show the onset of behavioral estrus. Beginning on Day 16 of their first estrous cycle, 42 crossbred gilts were observed at 0600, 1200, 1800, and 2400 h for the onset of their second estrus. Fifty-five percent of the gilts had shown onset of estrus by 0600 h. None of the gilts showed the onset of estrus from 0600 to 1200 h, whereas 24% and 21% of the gilts had shown onset of estrus by 1800 and 2400 h, respectively. Chi-square analysis demonstrated that more (P < 0.025) gilts had shown onset of estrus by 0600 than by 1200, 1800, and 2400 h. When the data were combined for estrous checks by 0600 and 1800 h, 76% of the gilts had their onset of estrus by 0600 h as compared to 24% of the gilts by 1800 h (P < 0.005). In conclusion, more gilts had shown onset of estrus by 0600 h than at any other 6-h period.

Journal Article↗

Pathology of surgery after induction chemotherapy: an analysis of resectability and locoregional control.

At the Dana-Farber Cancer Institute Head and Neck Cancer Clinic, 114 previously untreated patients with advanced squamous cell carcinoma of the head and neck (17% stage III; 83% stage IV) were managed with induction chemotherapy using cis-platinum, bleomycin, and methotrexate, followed by definitive extirpative surgery and/or radiation therapy. The present report evaluates this group from a surgical and surgical pathology standpoint. The following aspects are evaluated: predictability of, and conversion to, resectability during induction chemotherapy; ease of surgical technique and intraoperative assessment; patterns of pre-op and post-op risks and complications; gross and histopathologic observations of the extent and character of residual primary and nodal disease, particularly after a response to chemotherapy; patterns of locoregional control or failure related to treatment variables. The issues subsequently addressed include: how does chemotherapy affect the operative candidacy and resectability of proposed surgical patients? Could, or should surgery be eliminated in the management of some patients treated with induction chemotherapy? Can less radical surgery be contemplated in patients significantly "downstaged" by prior chemotherapy treatment? Is increased locoregional or distant metastatic control observed in these patients? What is the role of surgery in the responder to chemotherapy?

Antineoplastic Combined Chemotherapy Protocols↗

Effect of lactation and rebreeding phase energy intake on primiparous and multiparous sow performance.

Fifty-three primiparous sows were used to study the effects of a high-energy, fat-supplemented diet on sow lactation and rebreeding performance. Sows received either a low [Lo, 12.5 Mcal metabolizable energy (ME)/d] or high (Hi, 16.0 Mcal ME/d) energy sorghum-soybean diet during a 28-d lactation. At weaning, sows were randomly allotted, within lactation treatment, to a low (lo, 5.54 Mcal ME/d) or high (hi, 9.61 Mcal ME/d) energy sorghum-soybean diet until the day of first postweaning estrus. Primiparous sows fed Lo weaned larger (P less than .05) litters than sows fed Hi; however, average pig weight was not affected by lactation treatments. Primiparous sows fed Hi had more backfat at weaning (P less than .01) than Lo sows. In contrast, sow weight was not affected by dietary treatments. Neither lactation nor rebreeding treatments influenced days to rebreeding; however, an interaction (P less than .01) was observed. Mean days from weaning to rebreeding for Lolo, Lohi, Hilo and Hihi sows were 10.0, 7.6, 6.9 and 17.1, respectively. Forty sows were maintained on the same dietary treatments during their second parity. Sows receiving Lo during their second parity farrowed and weaned more (P less than .05) pigs than Hi sows. Multiparous sows fed Hi nursed heavier (P less than .05) pigs on d 21 of lactation and at weaning compared with Lo sows. Sows fed Hi were heavier (P less than .05) and had more (P less than .01) backfat at weaning of their second litter compared to Lo sows. Days to postweaning estrus were not affected by lactation or rebreeding diets. Mean length of the second parity rebreeding interval for Lolo, Lohi, Hilo and Hihi sows was 6.2, 10.2, 7.0 and 10.5 d, respectively. These results suggest that feeding levels during lactation of 12.5 Mcal ME/d or higher supported adequate rebreeding performance. Postweaning feeding levels did not influence days to first estrus. Feeding a high energy diet continuously throughout the lactation and rebreeding phases in primiparous sows may lengthen the postweaning interval to estrus.

Animals↗

Combined modality treatment of head and neck cancer with cisplatin, bleomycin, methotrexate-leucovorin chemotherapy.

The multidisciplinary treatment results of 114 patients with advanced, untreated Stage III and IV squamous cell carcinoma of the head and neck region are reported. Induction chemotherapy with two cycles of cisplatin 20 mg/m2/day intravenous bolus days 1 through 5, bleomycin 10 mg/m2/day as a continuous infusion days 3 through 7, and methotrexate 200 mg/m2 intravenous bolus on days 15 and 22 with leucovorin rescue was utilized before definitive surgery and/or radiation therapy. The total response rate was 78% with 30 (26%) patients achieving complete response and 59 (52%) patients achieving partial response. Patient age, performance status, histologic grade of tumor, and tumor site did not predict response to chemotherapy. Induction chemotherapy was well tolerated with myelosuppression and nephrotoxicity being dose-limiting in a few patients. The toxicity of subsequent local treatment with surgery and/or radiation is reported with an analysis of local treatment failures. A strong correlation was noted between local control of tumor and postchemotherapy tumor size before local treatment.

Adult↗

Treatment of perineural metastasis from squamous carcinoma of the skin with aggressive combination chemotherapy and irradiation.

Perineural metastasis from squamous cell carcinoma is quite rare. The treatment of such metastasis in the head and neck region is difficult due to base of skull or intracranial involvement by tumor. Surgery and radiotherapy may provide local control, but patients often fail distantly. We present a patient with squamous cell carcinoma presenting with perineural metastasis who was successfully treated with combination chemotherapy and definitive radiation therapy. Suggestions of therapeutic management are made of this uncommon clinical problem.

Aged↗

Relative sensitivity of six estuarine fishes to carbophenothion, chlorpyrifos, and fenvalerate.

The acute toxicity (96-hr LC50) of carbophenothion, chlorpyrifos, and fenvalerate to six estuarine fishes was determined in flow-through laboratory tests. The atherinid fishes (Menidia menidia, M. peninsulae, M. beryllina, and Leuresthes tenuis) consistently were among the most sensitive species tested and were similar to each other in their sensitivity to pesticides. The sensitivity of sheepshead minnows (Cyprinodon variegatus) to carbophenothion was the same as that of the atherinids. For fenvalerate, the sheepshead minnow LC50 was an order of magnitude greater than that of the most sensitive atherinid, whereas the LC50 for chlorpyrifos and sheepshead minnows was two orders of magnitude greater. Gulf toadfish (Opsanus beta) were the least sensitive fish tested with carbophenothion and chlorpyrifos and their 96-hr LC50 for fenvalerate ranked between the LC50 for sheepshead minnows and atherinids. Test results were compared to acute toxicity data for other estuarine fishes and invertebrates.

Animals↗

Treatment complications after sequential combination chemotherapy and radiotherapy with or without surgery in previously untreated squamous cell carcinoma of the head and neck.

One hundred consecutive patients with previously untreated advanced squamous cell carcinoma of the head and neck were treated with induction combination chemotherapy followed by definitive surgery and/or radiotherapy, and were evaluated for radiotherapy related toxicity. The induction regimen consisted of cisplatin, bleomycin and methotrexate/leucovorin. Acute toxicity consisted predominantly of mucositis and weight loss, and was mild or moderate by degree in 94% of patients. Six percent of patients experienced severe or life threatening acute toxicities. Two acute toxic deaths were noted in this series, one from a combination of mucositis, weight loss and infection and one from hypoglycemia of unknown origin. Thirty-five percent of patients had radiation treatment interrupted briefly because of acute toxicity. Toxicity was greatest in patients who were nonresponders to induction chemotherapy and such may have been related to the continued presence of advanced tumor. Radiotherapy dose, surgical intervention and age did not have an impact on the presence or degree of acute toxicity. Late toxicities included: hypothyroidism in 32% of patients tested: osteoradionecrosis in 5% of patients, associated primarily with a composite resection (4 of 5 cases); and soft tissue ulcerations in 3%. Taken together, these data indicate that induction combination chemotherapy did not significantly increase the toxicity of subsequent radiotherapy with or without surgery.

Antineoplastic Combined Chemotherapy Protocols↗