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Biomedical subjects

R G Martin

Publications and source records attributed to R G Martin.

At least 73 records · Page 4Linked to original sources
PubMed1986

Facial bone augmentation using Bioglass in dogs.

In the quest for a material other than autograft and homograft bone for use in facial augmentation and replacement, materials scientists have developed numerous inert materials, some of which have a porous structure allowing scar tissue ingrowth to aid in stabilization of the implant. This study investigates a bioactive, nonporous, transparent glass (Bioglass) in a dog model for use in facial bone augmentation. In 18 dogs studied in three groups at 1, 3, and 6 months, Bioglass implants developed a bond to bone or soft tissue in 54 of 72 instances (75% of the time). Poor bonding of mobile chin implants and the loss of three implants due to infection accounted for all but three of the 18 failures. Histologic evaluation revealed no untoward tissue response. Because of the tissue bonding ability and amenability to contouring with a diamond bur at the time of surgery, Bioglass is promising as a graft material for facial bone augmentation.

Alveolar Ridge Augmentation↗
PubMed1986

Active specific immunotherapy of Dukes B2 and C colorectal carcinoma: comparison of two doses of the vaccine.

The ability of active specific immunotherapy to enhance immune responses to autologous tumor-associated antigens (TAA) and to prolong the disease-free interval was evaluated in patients with Dukes B2 and C colorectal carcinoma who had undergone potentially curative resections. Patients were sensitized in the early postoperative period with irradiated autologous adenocarcinoma cells mixed with bacillus Calmette-Guérin (BCG) to yield either a low-dose vaccine (3 X 10(6) tumor cells) or a high-dose vaccine (1 X 10(7) tumor cells). Six of seven patients who received the low-dose vaccine developed delayed-type hypersensitivity (DTH) responses to autologous tumor cells upon completion of the vaccination, whereas all four patients receiving high-dose vaccine displayed a positive DTH response. However, DTH responses to autologous TAA waned within 3 months in all patients receiving the low-dose vaccine; DTH responses persisted for 3 months in three of the four high-dose vaccine patients. In vitro lymphoproliferative responses to TAA correlated with DTH responses to autologous tumor cells. Active specific immunotherapy appeared to induce specific immune responses either in vitro or in vivo to autologous TAA because it did not induce responses to autologous mucosa cells. There were no complications caused by BCG or tumor cells. This series demonstrates that active specific immunotherapy is a nontoxic treatment that augments immunity to autologous TAA.

Adult↗
PubMed1986

Malignant tumors of the small intestine.

The four main histologic categories of malignant small intestine tumors are (1) adenocarcinoma, (2) sarcoma, (3) carcinoid, and (4) lymphoma. Signs and symptoms may be chronic or acute and include bleeding, obstruction, pain, and weight loss. When chronic, the symptoms are so vague that early diagnosis is difficult. Often the diagnosis is made only at the time of surgery. Treatment is segmental resection of intestine with adequate margin of the tumor and resection of the regional lymph nodes. Prognosis is evaluated by tumor extension through the bowel wall and lymph node metastasis. The 5-year survival rates are low except for carcinoid and lymphomatous lesions.

Adenocarcinoma↗
PubMed1986

Nucleosome phasing on a DNA fragment from the replication origin of simian virus 40 and rephasing upon cruciform formation of the DNA.

Nucleosomes were reconstituted in vitro from a fragment of DNA spanning the simian virus 40 minimal replication origin. The fragment contains a 27-base-pair palindrome (perfect inverted repeat). DNA molecules with stable cruciform structures were generated by heteroduplexing this DNA fragment with mutants altered within the palindromic sequence (C. Nobile and R. G. Martin, Int. Virol., in press). Analyses of the structural features of the reconstituted nucleosomes by the DNase I footprint technique revealed two alternative DNA-histone arrangements, each one accurately phased with respect to the uniquely labeled DNA ends. As linear double-stranded DNA, a unique core particle was formed in which the histones strongly protected the regions to both sides of the palindrome. The cruciform structure seemed to be unable to associate with core histones and, therefore, an alternative phasing of the histone octamer along the DNA resulted. Thus, nucleosome positioning along a specific DNA sequence appears to be influenced in vitro by the secondary structure (linear or cruciform) of the 27-base-pair palindrome. The formation of cruciform structures in vivo, if they occur, might therefore represent a molecular mechanism by which nucleosomes are phased.

Animals↗
PubMed1986

Stable stem-loop and cruciform DNA structures: isolation of mutants with rearrangements of the palindromic sequence at the simian virus 40 replication origin.

With the objective of generating DNA molecules that form stable stem-loop structures or cruciform structures in solution, we have altered the palindromic sequence at the Simian Virus 40 (SV40) replication origin. These alterations include: deletion of 18 of the 27 base pairs (bp) in the 13-bp inverted repeat; deletion of 26 of the 27 bp; substitution of the entire 27 bp with a totally different 26-bp sequence containing a 13-bp inverted repeat; and substitution of the 27 bp with an 8-bp sequence containing a 4-bp inverted repeat. The DNA from these mutants was purified. Mutant DNAs were hybridized to wild-type SV40 DNA or to each other, and the heteroduplexes were purified. The predicted structures were verified by S1 and restriction endonuclease digestion. The mutants - the heteroduplexes have not been tested - are capable of complementing tsA mutants and/or transforming mouse cells.

Autoradiography↗
PubMed1986

Relationship of erythrocyte polyamine levels and growth rate of transplantable tumors in rats.

Varying levels of polyamines in the urine, plasma, and erythrocytes (RBC) of cancer patients have been demonstrated. The growth rate of the tumor has been suggested as a primary factor which determines whether the polyamine levels in urine are elevated. To further evaluate tumor size and growth rate as variables affecting polyamine levels in physiological fluids, the effect of a transplantable fibrosarcoma and colon tumor on the RBC polyamine levels of Fischer 344 rats was determined. The tumors were implanted s.c. and grew without metastasis or spontaneous regression. The fibrosarcoma grew exponentially up to a weight of approximately 69 +/- 15 (SD) g and was associated with a linear increase in RBC polyamine levels compared with that of non-tumor-bearing rats. RBC putrescine, spermidine, and spermine levels were significantly elevated at tumor weights of 12.5 +/- 1.4, 20.4 +/- 3.8, and 33.2 +/- 5.0 g, respectively. The respective polyamines increased consistently thereafter until the tumor weight was 57.8 +/- 5.8 g. In contrast with the fibrosarcoma, the colon tumor grew exponentially only to a weight of 9.2 +/- 4.7 g, at which time the growth rate of the tumor began to decrease (time T of the Gompertz model). RBC polyamine levels of rats with the colon tumor showed only a transient increase. RBC putrescine levels were significantly increased at a tumor weight of 12.9 +/- 1.2 g and spermidine at a tumor weight of 17.4 +/- 0.2 g. RBC spermine levels were significantly elevated at both tumor weights; thereafter, all RBC polyamine levels returned to normal. Host cachexia was evident when the fibrosarcoma and colon tumors weighed 12.5 +/- 0.9 and 7.2 +/- 2.6 g, respectively. The polyamine levels of the fibrosarcoma differed significantly from that of the colon tumor. These levels, however, did not correlate with the exponential growth rates. The results suggest that the tumor is the major source of elevated RBC polyamines. The data also suggest that the tumors must be rapidly growing for the elevation in polyamines to occur. This may partly explain why patients with extensive neoplastic disease that may have surpassed time T in the Gompertz model do not manifest abnormal polyamine levels.

Animals↗
PubMed1986

Mechanisms of synergism between arteriolar embolization and hyperthermia in a rabbit V-2 model of solitary hepatic metastasis.

In a V-2 model of solitary hepatic metastasis, residual tumor was histologically identified in the treatment field in only three of 14 (21%) animals subjected to microsphere embolization of tumor arterioles plus focal (43 degrees C, 40 min) hyperthermia compared with seven of ten (70%) subjected to focal (43 degrees C, 40 min) hyperthermia alone (P less than or equal to 0.05), five of seven (71%) (P less than or equal to 0.05) treated by occlusion plus sham heating, and five of five (100%) (P less than or equal to 0.01) sham-treated controls. Prior occlusion tended to reduce the radiofrequency power required for heat up and steady-state temperature maintenance of tumors (P less than or equal to 0.09 and P less than or equal to 0.06, respectively) and reduced the cooling rate after heating compared to unoccluded tumors (P less than or equal to 0.02) but did not affect mean time to temperature, maximum and minimum temperature measured at the tumor-normal tissue interface, and animal core temperature compared with that of the hyperthermia alone treatment group. In ten other animals with hepatic V-2 tumors of comparable size subjected to focal hyperthermia plus or minus arteriolar embolization, temperatures were continuously monitored at four additional intratumor sites in a fixed geometric orientation around the heating probe. No significant differences were noted in maximum and minimum temperatures in comparably oriented probes over a 40-min heating period between the hyperthermia and the occlusion-hyperthermia treatment groups. In five other animals with solitary V-2 hepatic implants, comparable microembolization plus or minus focal tumor heating to 43 degrees C, 40 min, did not significantly reduce tumor interstitial pH compared with pretreatment values. This study reproduces previously observed synergism between arteriolar embolization and hyperthermia but suggests the mechanism may be unrelated to observable differences in intratumor pH and thermal profile and may result from other mechanisms, perhaps by mimicking the angioocclusive effects of hyperthermia itself.

Animals↗
PubMed1985

Focal heating of V-2 tumors with a hybrid radiofrequency applicator.

A hybrid radiofrequency heating system previously reported to produce highly focused heating patterns at less than or equal to 10 cm depth in phantom models was utilized to selectively heat hypervascular, heat resistant rabbit V-2 tumors implanted in the left hindlimb. Spheroidal heating patterns 3 to 4 cm in diameter with minimal temperatures of 43 degrees C to 46 degrees C in two non-field perturbing probes at opposing edges of the tumor were consistently produced; however, temperature maxima 0.5 +/- 0.4 to 8.6 +/- 5.9 degrees C above minimum target temperatures of 43 degrees C and 46 degrees C, respectively, were observed. This led to both tumor regressions and adjacent normal tissue damage in some animals. These findings suggest this system may have application to selective heating of deep seated tumors, but that problems related to accurate thermal mapping and to intratumor temperature distribution must first be resolved.

Animals↗
PubMed1985

Consistency of care in an intensive care nursery staffed by nurse clinicians.

Variables related to both the process and outcome of newborn intensive care were studied to evaluate care consistency in a level 3 Newborn Intensive Care Unit (NICU) where neonatal nurse clinicians function in a role usually held by pediatric house officers. In routine delivery of intensive care, there were no statistically significant diurnal variations in the overall mortality, maintenance of intravenous infusions, tolerance of oral feedings, or respiratory care except a decrease in frequency of blood gas sampling during the weekday days as compared with nights. Our data suggest that a tertiary NICU in which medical coverage by neonatologists is supplemented by carefully trained and supervised neonatal nurse clinicians provides a consistent level of care that does not vary between night and day or day of the week.

Blood Gas Analysis↗
PubMed1985

Management of inflammatory carcinoma of the breast. A combined modality approach.

From May 1973 to December 1981, 63 patients with inflammatory carcinoma of the breast were treated with a doxorubicin-containing chemotherapy regimen (FAC). After a median of three cycles of FAC, 41 patients received primary therapy with irradiation; more recently, 21 had mastectomy as primary therapy. One patient relapsed following a treatment delay and did not receive local therapy. Fourteen of 21 patients who underwent mastectomy had subsequent consolidation therapy with irradiation. At median follow-up of 60 months, median relapse-free survival (RFS) and survival were 24 and 43 months, respectively. The initial site of recurrence was locoregional in eight patients (20%). In addition, two of seven uncensored patients (18%) who suffered initial recurrence in the contralateral breast remained disease-free at 28 and 55 months with further surgery. While no locoregional recurrences were seen in the 14 mastectomy patients who completed comprehensive irradiation, no RFS nor survival advantage was noted for either initial local therapy. Sixteen patients with dermal lymphatic carcinomatosis and 10 patients with negative skin biopsies had median RFS of 31 and 46 months, respectively (p = 0.45). Median RFS was 36 months in patients greater than or equal to 50 years of age and 19 months in patients less than 50 (p = 0.05). Response to FAC was the most significant predictor of RFS and survival. Patients who achieved complete or partial remission (PR) with induction FAC as compared to patients who achieved less than PR had median RFS of 31 vs. 19 months (p = 0.01) and median survivals of 60 vs. 27 months (p = 0.05), respectively. Categorization of patients according to clinical, mammographic, and pathologic criteria facilitated identification of potential long-term responders. With combined modality approach to inflammatory carcinoma of the breast, we can expect an estimated 31% of patients to be relapse-free at 5 years after treatment.

Adult↗
PubMed1985

Selective occlusion and focal hyperthermia therapy of V-2 tumors in the rabbit hindlimb.

Utilizing technology recently developed in our laboratory, hypervascular, heat-resistant V-2 tumors growing in the rabbit hindlimb were variously subjected to selective vascular occlusion by embolization with Dextran M microspheres and focal hyperthermia to minimum intratumor temperatures of 43 degrees C X 40 minutes (OH), focal 43 degrees C X 40 minutes hyperthermia alone (H), selective occlusion plus sham hyperthermia (O), and sham treatment. Regional toxicity observed consisted of skin burns and muscle fibrosis in the H and OH groups and peripheral embolization in the O alone group. Tumors subjected to a single OH treatment had significantly reduced growth rate over a 28-day period of observation compared with all other treatment groups and sham-treated controls (P less than or equal to .05). Our findings suggest that the combination of selective vascular embolization and focused hyperthermia may be useful in therapy of hypervascular, heat-resistant human tumors in anatomic locations where selective occlusion and relatively intense focal heating can be performed. The regional toxicity encountered in this model reemphasizes the need for extensive thermal mapping over the heated region.

Animals↗
PubMed1985

Formation of a cruciform structure at the simian virus 40 replication origin abolishes T-antigen binding to the origin in vitro.

Heteroduplex DNA molecules were formed by annealing an intact simian virus replication origin-containing fragment to a mutant derivative lacking the indigenous wild-type 27-base-pair (bp) inverted repeat within this structure and containing a nonhomologous 26-bp inverted repeat sequence in its place. Results of restriction enzyme and S1 endonuclease cleavage analyses strongly suggested that a 13-bp stem-loop structure formed at the site of nonhomology between these two DNAs. This structure lies within the boundary of simian virus 40 T-antigen-binding site 2, and its presence inhibited T-antigen binding to that sequence but not to an adjacent higher-affinity binding site (site 1). Therefore, the conformation of sequences within an otherwise intact T-antigen-binding site can have major effects upon T-antigen binding there.

Antigens, Viral, Tumor↗
PubMed1985

Cloning of nascent monkey DNA synthesized early in the cell cycle.

To study the structure and complexity of animal cell replication origins, we have isolated and cloned nascent DNA from the onset of S phase as follows: African green monkey kidney cells arrested in G1 phase were serum stimulated in the presence of the DNA replication inhibitor aphidicolin. After 18 h, the drug was removed, and DNA synthesis was allowed to proceed in vivo for 1 min. Nuclei were then prepared, and DNA synthesis was briefly continued in the presence of Hg-dCTP. The mercury-labeled nascent DNA was purified in double-stranded form by extrusion (M. Zannis-Hadjopoulos, M. Perisco, and R. G. Martin, Cell 27:155-163, 1981) followed by sulfhydryl-agarose affinity chromatography. Purified nascent DNA (ca. 500 to 2,000 base pairs) was treated with mung bean nuclease to remove single-stranded ends and inserted into the NruI site of plasmid pBR322. The cloned fragments were examined for their time of replication by hybridization to cellular DNA fractions synthesized at various intervals of the S phase. Among five clones examined, four hybridized preferentially with early replicating fractions.

Animals↗
PubMed1985

Properties of some monkey DNA sequences obtained by a procedure that enriches for DNA replication origins.

Twelve clones of monkey DNA obtained by a procedure that enriches 10(3)- to 10(4)-fold for nascent sequences activated early in S phase (G. Kaufmann, M. Zannis-Hadjopoulos, and R. G. Martin, Mol. Cell. Biol. 5:721-727, 1985) have been examined. Only 2 of the 12 ors sequences (origin-enriched sequences) are unique (ors1 and ors8). Three contain the highly reiterated Alu family (ors3, ors9, and ors11). One contains the highly reiterated alpha-satellite family (ors12), but none contain the Kpn family. Those remaining contain middle repetitive sequences. Two examples of the same middle repetitive sequence were found (ors2 and ors6). Three of the middle repetitive sequences (the ors2-ors6 pair, ors5, and ors10) are moderately dispersed; one (ors4) is highly dispersed. The last, ors7, has been mapped to the bona fide replication origin of the D loop of mitochondrial DNA. Of the nine ors sequences tested, half possess snapback (intrachain reannealing) properties.

Animals↗
PubMed1985

Myocardial surgical revascularization after streptokinase treatment for acute myocardial infarction.

Eighty-six patients admitted with evolving myocardial infarction within 6 hours of symptom onset were treated with streptokinase. Thirty-nine received intracoronary streptokinase, and 47 received intravenous streptokinase. There were no streptokinase-related complications. Twenty-three patients treated with intracoronary streptokinase and 28 patients receiving intravenous streptokinase underwent coronary artery bypass grafting. On admission, 16 patients receiving intracoronary streptokinase had electrocardiographic evidence of anterolateral evolving myocardial infarction and seven had evidence of inferior evolving myocardial infarction. Time from first symptom to intracoronary streptokinase was 4.4 +/- 1.6 hours. In seven patients, intracoronary streptokinase failed to open the obstructed coronary. All developed severe left ventricular hypokinesia in the area supplied by that coronary artery. In spite of recanalization, nine of 14 patients developed severe hypokinesia in the supplied area, and one an apical aneurysm. Four patients developed mild to moderate hypokinesia, and one had no left ventricular damage. On admission, 14 patients receiving intravenous streptokinase had electrocardiographic evidence of anterolateral evolving myocardial infarction and four had evidence of inferior evolving myocardial infarction. Time from first symptom to intravenous streptokinase was 3.2 +/- 1.5 hours. In seven patients, intravenous streptokinase failed to open the coronary, and all developed severe hypokinesia of the supplied area, with formation of apical left ventricular aneurysm in three. In 21 patients, intravenous streptokinase opened the artery. Eighteen angiographies performed 9.6 +/- 7.9 days after therapy showed a normal left ventricle in eight patients, moderate hypokinesia in seven, and severe hypokinesia in three. Time from first symptom to therapy was shorter in the patients receiving intravenous therapy (p less than 0.01). Coronary artery bypass grafting and four resections after left ventricular aneurysm were performed without operative death. Two patients receiving intracoronary therapy died in the hospital, and one died 2 months later from arrhythmias. Freedom from angina and rehabilitation (New York Heart Association Class I) were achieved in 69.5% of patients receiving intracoronary streptokinase and in 75% of patients receiving intravenous streptokinase. Thus streptokinase-induced thrombolysis salvages myocardium, and the intravenous route seems as effective as the intracoronary. Advantages of the former are earlier administration that might increase myocardial salvage, no invasive procedure, and lesser cost.

Adult↗
PubMed1984

Stages IE and IIE non-Hodgkin's lymphomas of the stomach. Comparison of treatment modalities.

Seventy-nine patients with Stages IE and IIE non-Hodgkin's lymphomas of the stomach were treated between 1953 and 1980. The histopathologic classification was as follows: diffuse large cell, 61 (of which 23 were immunoblastic sarcomas [plasmacytoid]); diffuse well-differentiated lymphocytic, 6; diffuse mixed, 1; undifferentiated non-Burkitt's, 1; nodular, 9; and unclassifiable, 1. Thirty-five patients had Stage IE disease and 44 had Stage IIE. Treatment modalities included surgery, radiotherapy, chemotherapy, and combinations thereof. Sixty-six patients had a laparotomy for diagnosis and/or management. Of these, only 42 had a gastrectomy. The stomach was considered to be unresectable in the other 24 patients. There were 5 postoperative deaths among 31 patients who had a laparotomy or gastrectomy at our institution. The overall 5-year actuarial survival was 56%; the disease-free survival was 54%. For patients with Stage IE disease the survival was 76%, and for those with Stage IIE, 42%. Promising results were obtained in 13 patients who were treated on a multimodality program consisting of four cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus bleomycin (Bleo), which was alternated with involved field radiotherapy. All 13 patients had no evidence of disease as of this report. Only one patient had a relapse (Waldeyer's ring), and he was salvaged with radiotherapy. Six of these 13 were diagnosed by endoscopic biopsy and did not have a laparotomy, 3 were found to have unresectable disease at laparotomy, and 4 had a resection. Biopsy with the flexible fiberscope and treatment with CHOP-Bleo and radiotherapy can avoid the morbidity and mortality of gastrectomy.

Adult↗