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Biomedical subjects

N Newman

Publications and source records attributed to N Newman.

At least 73 records · Page 4Linked to original sources

Structure-function relationship of human spinal ligaments.

A combination of light, scanning and transmission electron microscopy was used to investigate the morphology and ultrastructure of normal human spinal ligaments sampled from adult surgical specimens. The ligamenta flava consist mostly of dense elastic fibers, whereas the supraspinous and interspinous ligaments are preponderantly collagenous. In all ligaments, the collagen fascicles are characterized by a regular crimp structure. The inner collagen fibers of interspinous ligaments tend to be oriented parallel to the spinous processes while those of the peripheral layers run in postero-cranial direction. The presence of proteoglycan filaments is clearly demonstrated in all of the ligaments examined. They are mainly located at the d band of the collagen fibrils. These findings are discussed in relation to the function of the posterior ligamentous system. It is suggested that the interspinous ligaments are able to transmit tension from the thoracolumbar fascia to the spine. Finally, the spinal ligaments are thought to be involved in the control mechanism of the spine.

Adolescent↗

A phase II trial of iproplatin (CHIP) in previously treated advanced breast cancer.

Iproplatin (CHIP) was administered to 35 previously treated women with metastatic adenocarcinoma of the breast. The drug was given at a dose of 45 mg/m2 intravenously for 5 consecutive days and was repeated every 28 days. In this trial, there was one partial response and two patients with stable disease out of 29 evaluable patients. The median duration of response in patients with either a partial response or stable disease was 4.8 months. Myelosuppression was the major toxicity, 11 patients had severe thrombocytopenia and 3 severe neutropenia. Mild renal insufficiency, anemia, and nausea and vomiting were also noted. Iproplatin has limited activity in heavily pretreated women with advanced breast carcinoma; further studies in patients less heavily treated may show an improved response rate.

Adenocarcinoma↗

Phase II study of iproplatin (CHIP) in previously treated small-cell lung cancer.

Eighteen patients with previously treated extensive small-cell carcinoma of the lung were entered into a Phase II study employing iproplatin (CHIP), a cis-platin analog. Patients had received a mean of two prior chemotherapeutic regimens. Fifty-five percent had received prior cis-platinum and 33% had received prior radiation therapy. CHIP (225 mg/m2) was administered by intermittent intravenous infusion over 30 min for 5 days of a 28-day cycle without prehydration. Sixteen patients with Zubrod performance scores of less than or equal to 3 received 27 courses of therapy (mean 1.7, range 1-6). One partial response of 167 days duration was observed, with complete regression of involved lymph nodes and stabilization of nonevaluable disease in the chest. Six patients had stable disease following one cycle of CHIP, but all progressed following a second cycle of drug. The main toxicity was myelosuppression with prominent thrombocytopenia. Median survival was 75 days from initiation of therapy. In this group of heavily pretreated patients with advanced disease, iproplatin has only minimal activity as a single agent and does not show non-cross-resistance with cis-platinum.

Aged↗

The use of neuroendocrine immunoperoxidase markers to predict chemotherapy response in patients with non-small-cell lung cancer.

Small-cell lung cancer (SCLC), a chemotherapy-responsive disease, is characterized by neuroendocrine properties. In contrast, non-small-cell lung cancer (NSCLC) is at best moderately responsive to chemotherapy, and only 10% to 20% of cases demonstrate neuroendocrine properties. The present study is a retrospective analysis of the use of immunoperoxidase markers for neuron-specific enolase (NSE), Leu-7, and chromogranin A in NSCLC patients treated with chemotherapy. It was designed to determine if the presence of neuroendocrine markers predict for response to chemotherapy. The diagnostic slides and blocks were obtained on 52 NSCLC patients who were treated with chemotherapy (26 responders and 26 nonresponders). Immunoperoxidase studies were performed, and slides were scored without knowledge of the patient's response. Markers were positive in responders and nonresponders, respectively, as follows: NSE, 14 of 26 (54%) versus seven of 26 (27%), P = .04; Leu-7, 11 of 25 (44%) versus five of 26 (19%), P = .08; and chromogranin A, three of 26 (12%) versus 0 of 26 (0%), P = .71. Two markers were positive in 10 of 26 responders (38%) and 0 of 26 nonresponders (0%), P less than .01. Responders with two or more positive markers showed superior survival (median, 79 weeks) compared with responders with fewer than two positive markers (median, 51 weeks) and nonresponders (median, 27 weeks). These data suggest that the presence of neuroendocrine markers in NSCLC is associated with an increased likelihood of response to chemotherapy and may add to the standard parameters (performance status, weight loss) used to select patients for chemotherapy.

Adult↗

Phase I trial of recombinant interleukin-2 and recombinant beta-interferon in refractory neoplastic diseases.

Interleukin-2 (IL-2) and beta-interferon (beta-IFN) are cytokines with profound immunobiological effects on T-cell and natural killer (NK) cell activity; IL-2 also induces lymphokine-activated killer (LAK) cell cytotoxicity in humans. Both lymphokines induce antineoplastic activity against several refractory tumors. This Phase I study of 50 patients assessed the toxicities, maximally tolerated dose (MTD), effects on certain immune effector cells, pharmacokinetics of IL-2, and development of antibodies to the combination of subcutaneously administered IL-2 and intravenously administered beta-IFN. Fever was common. Indomethacin reduced the incidence and severity of fever and was necessary to prevent it from becoming dose-limiting. Hypotension occurred but never required pressors or produced complications. Constitutional symptoms, local skin toxicity at the site of IL-2 injection, generalized desquamation, eosinophilia, nausea, and vomiting were also observed. One patient had reversible renal dysfunction. Two patients experienced drug-related dyspnea without evidence of capillary leak syndrome; neither required intubation. Fluid retention and cardiotoxicity were not observed. The MTD was 5 x 10(6) U/m2 s.c. of IL-2 and 2 x 10(6) U/m2 i.v. of beta-IFN when given in combination. Enhancement of in vivo NK cell cytotoxicity and proliferation of T4+, T8+, and NK cells occurred. In vivo induction of LAK cell cytotoxicity was observed in three patients. Four patients developed nonneutralizing anti-IL-2 IgG antibodies, but none developed antibodies to beta-IFN. Peak IL-2 serum levels typically occurred 4 h following drug administration. Serum levels were within a factor of 3 of the peak level in the period studied, 1-6 h postinjection. No complete responses occurred. One patient with rectal cancer and one with transitional cell carcinoma each had a partial response, and 13 other patients (5 with renal cell, 4 with colorectal, and 4 other cancers) had stable disease. Induction of NK cell cytotoxicity was seen more commonly in patients with stable disease than in those with progressive disease. Combined administration of these agents is feasible with acceptable toxicity, and Phase II trials are warranted.

Adult↗

A light and electron microscopic study of spinal ligament innervation.

The innervation of the posterior ligamentous structures of the human lumbar spine was studied by light microscopy, scanning electron microscopy and transmission electron microscopy. Three types of nerve endings were recognized: free nerve endings, Paciniform corpuscles and Ruffini corpuscles. The free nerve endings, which are thought to act as nociceptors, were found in the superficial layers of all ligaments. A few free nerve endings were also identified within the supraspinous and interspinous ligaments. The Paciniform corpuscles were predominantly found in the supraspinous ligament. The Ruffini corpuscles were located in the interspinous and flaval ligaments. These findings suggest that the posterior ligamentous structures could be involved in the spinal control system.

Humans↗

Phase I--preliminary phase II trial of iproplatin, a cisplatin analogue.

Iproplatin was administered intravenously over 30 min daily for 5 consecutive days every 3 weeks to 80 evaluable patients with a variety of refractory solid tumor malignancies. Thrombocytopenia was the dose-limiting toxicity. Reversible drug-induced renal dysfunction was observed in 3 patients. One patient sustained mild ototoxicity but neurotoxicity was not encountered. Transient neutropenia, anemia, nausea, vomiting, diarrhea, elevations of liver enzymes, alopecia, and skin rash also occurred. The spectrum and severity of toxicity of iproplatin were found to differ from those of cisplatin. The maximally tolerated dose (MTD) was 45 mg/m2/day in patients who received prior chemotherapy and 65 mg/m2/day in those who did not. No complete responses occurred. Partial responses were obtained in 2/15 patients with colon cancer, 3/18 with breast cancer, 2/4 with carcinoma of unknown primary site and 1/2 with pancreatic cancer. Thirteen patients with lung (5), breast (4), colon (2), head and neck (1) and cervical (1) cancers had stable disease. Based on the different toxicity profiles between iproplatin and cisplatin and the possible antitumor efficacy of the former, phase II investigation of iproplatin has been initiated.

Adult↗

Neuroendocrine (Merkel cell) carcinoma of the vulva.

The clinical, histopathologic, and ultrastructural features of a primary cutaneous vulvar neuroendocrine neoplasm (Merkel cell carcinoma) are presented. This recently described tumor arises in the dermis and is often aggressive with metastasis to regional lymph nodes. Ultrastructural study of this case reveals morphologic similarities to normal cutaneous Merkel cells, including peripherally located dense-core neurosecondary-like granules, and immunohistochemical studies revealed ACTH within neoplastic cells. By light microscopy this tumor is readily confused with other primary or metastatic cutaneous neoplasms; therefore, the importance of electron microscopic examination is emphasized for definitive diagnosis of this unusual tumor.

Female↗

Phase II trial of iproplatin (CHIP) in previously untreated patients with colorectal cancer.

Nineteen previously untreated patients with colorectal cancer and measurable disease were treated with iproplatin (CHIP), 75 mg/m2 daily, for 5 days every 4 weeks for at least 2 courses. Toxicities included myelosuppression, mild nausea and vomiting, and rare mild nephrotoxicity. The dose-limiting toxicity was thrombocytopenia, which appeared to be cumulative. Dose reduction was frequently necessary. There were no toxic deaths. One partial response was observed, and four patients had stable disease for a median of 2 months. Iproplatin does not appear to have significant activity against colorectal cancer.

Adenocarcinoma↗

Neurohistology of lumbar spine ligaments.

A study was conducted to identify neural elements in the posterior ligaments of the lumbar spine by using a modified gold-chloride method. Three morphologic types of mechanoreceptors were identified: Ruffini corpuscles, Ruffini end organs, and pacinian corpuscles. Free nerve endings, which are thought to be responsible for pain production, were also demonstrated within the ligaments.

Adolescent↗