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Biomedical subjects

D H Johnson

Publications and source records attributed to D H Johnson.

At least 271 records · Page 15Linked to original sources
PubMed1988

Atypical carcinoid of the lung. A distinct clinicopathologic entity.

Eleven cases of atypical carcinoid (AC) of the lung were identified during an eight-year period. Their clinical features and treatment responses were contrasted with our experience at Vanderbilt with small cell lung cancer (SCLC) and a literature review of typical bronchial carcinoids (TC). Clinically, there were no features to distinguish AC from TC except for age at diagnosis (59 vs 49 years). Atypical carcinoid was similar to SCLC with respect to many clinical features, although female sex, absence of smoking history and localized disease at presentation were more common in AC. Pathologically, these tumors were distinguished by cellular atypia, necrosis, architectural disorder, or increased mitotic rate in the presence of a recognizable carcinoid pattern. Immunoperoxidase staining revealed no difference between AC and TC or SCLC. Atypical carcinoid of the lung represents a distinct clinicopathologic disease.

Adult↗
PubMed1987

Cloning of a Drosophila melanogaster adenine phosphoribosyltransferase structural gene and deduced amino acid sequence of the enzyme.

The Aprt locus of Drosophila melanogaster encodes the structural gene for adenine phosphoribosyltransferase (APRT). DNA cloned from microdissected salivary gland polytene chromosome region 62B7-12 was used in conjunction with chromosome walking and hybrid selection of mRNA to isolate the Aprt gene. Aprt lies at cytogenetic position 62B9 and is closely flanked by other genes of unknown function. Nucleotide sequencing shows that four APRT cDNAs have a common 5' terminus with an apparent cap consensus sequence but two different 3' sites of polyadenylation. The distribution of conserved amino acid sequences in APRT from vertebrates, insects and bacteria suggests that they may have shared a common ancestral gene for this ubiquitous enzyme.

Adenine Phosphoribosyltransferase↗
PubMed1987

Disseminated Merkel cell tumor. Treatment with systemic chemotherapy.

Four patients with disseminated Merkel cell tumors were treated with cyclophosphamide (C), doxorubicin (A), and vincristine (V). Two partial responses (PR) were noted and in one case disease remained stable. One of the patients who achieved a PR achieved a second PR when treated with VP-16 (E) and cis-platin (P) after progressive disease developed. Systemic chemotherapy appears capable of inducing objective responses in some patients with disseminated Merkel cell tumors.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Limited stage small cell lung cancer: analysis of clinical prognostic factors.

In an attempt to identify clinical features of prognostic value in patients with limited stage small cell lung cancer, we retrospectively reviewed the records and chest roentgenograms of 101 such patients seen at Vanderbilt University Hospital. All patients were treated with combination chemotherapy regimens of comparable efficacy with or without chest radiotherapy and/or surgical resection. Median survival for the 101 patients was 16 months; the three-year actuarial survival was 14%. Elevated serum LDH level at the time of diagnosis was predictive of improved survival by both univariate and multivariate analyses (P less than .01). Initial tumor volume (calculated from tumor measurements) on chest roentgenogram and clinical TNM stage were unrelated to survival. Until the prognostic significance of an elevated serum LDH level is confirmed by other investigators, we cannot recommend any modification in the current system for staging small cell lung cancer. Although patients with limited stage small cell lung cancer form a clinically heterogeneous group, they should continue to be treated uniformly.

Actuarial Analysis↗
PubMed1987

A randomized comparison of high-dose versus conventional-dose cyclophosphamide, doxorubicin, and vincristine for extensive-stage small-cell lung cancer: a phase III trial of the Southeastern Cancer Study Group.

To assess the effect of dose escalation in the treatment of small-cell lung cancer (SCLC), 298 patients with extensive-stage disease were treated with either conventional-dose cyclophosphamide (1,000 mg/m2), doxorubicin (40 mg/m2), and vincristine (1 mg/m2), (CDCAV); or high-dose cyclophosphamide (1,200 mg/m2), doxorubicin (70 mg/m2), and vincristine (1 mg/m2) (HDCAV). No dose attenuation was allowed during the initial three cycles of therapy in either treatment arm. All patients received CDCAV in cycles 4 through 6, during which time dosages were adjusted according to granulocyte and platelet nadirs. No additional chemotherapy was administered until disease progression or relapse was documented. Complete responses were more frequent with HDCAV (22% v 12%; P = .045). However, overall response rate (63% v 53%) and median survival (29.3 v 34.7 weeks) were not significantly different (P greater than .05). HDCAV was substantially more toxic than CDCAV, causing more episodes of life-threatening leukopenia (ie, granulocytes less than 500/microL; 79% v 40%; P less than .05) and infections (15% v 4%; P less than .05). Dose intensification of cyclophosphamide and doxorubicin during induction chemotherapy did not produce any survival benefit compared with conventional dosages of these agents in SCLC patients with extensive-stage disease.

Adult↗
PubMed1987

High-dose induction chemotherapy with cyclophosphamide, etoposide, and cisplatin for extensive-stage small-cell lung cancer.

To exploit possible dose-response and combination drug synergism, 20 previously untreated patients with extensive-stage small-cell lung cancer (SCLC) received one or two courses of high-dose induction chemotherapy consisting of cyclophosphamide (100 mg/kg), etoposide (1,200 mg/m2), and cisplatin (120 mg/m2) (HDCEP). HDCEP was followed by four cycles of standard-dose cyclophosphamide (1,000 mg/m2), doxorubicin (40 mg/m2), and vincristine (1.4 mg/m2) (CAV). Response was determined after HDCEP and following CAV. Reevaluation included repeat bronchoscopy and chest computerized tomography (CT), as well as repetition of all initially abnormal studies. All patients were evaluable for response and toxicity. Overall response to HDCEP was 90%, with a complete response (CR) rate of 65% (95% confidence limits, 44% to 86%) and a partial response (PR) rate of 25% (95% confidence limits, 6% to 44%). All patients either maintained or improved their initial response while receiving CAV. Median duration of response was 6 months (range, 2 to 12 months) and median survival was 9.5 + months (range, 2 to 21 + months). All 37 courses of HDCEP were associated with leukopenia (less than 1,000/microL), 92% with thrombocytopenia (less than 20,000/microL), and 84% with fever of greater than 38.5 degrees C. Additional toxicities included bacteremia (24%), nausea and emesis (59%), mucositis (57%), diarrhea (38%), and hemorrhagic cystitis (5%). There were two treatment-related deaths due to infection. A third patient died 4 months after completing HDCEP with pulmonary fibrosis. Although response duration and median survival were not improved, HDCEP produced a high CR rate in ambulatory patients with extensive-stage SCLC.

Aged↗
PubMed1987

Postchemotherapy resection of residual tumor in limited stage small cell lung cancer.

To determine the feasibility of post-chemotherapy resection of residual tumor in small cell lung cancer, 24 selected patients with limited-stage disease were evaluated for exploratory thoracotomy. All 24 patients achieved partial or complete clinical response to chemotherapy and were considered adequate medical candidates for surgical resection. Fifteen patients underwent a lobectomy or pneumonectomy, 13 of whom had residual tumor in the resected specimen. Of the nine remaining patients, seven had no tumor found on biopsy at thoracotomy and two had unresectable mediastinal node involvement. No chemotherapy was administered postoperatively in any patient until disease progression or relapse was documented. Median survival for the entire group was 19 months and did not differ according to the surgical procedure performed. Nineteen patients had relapse. Patients undergoing biopsy only recurred locally in six of seven cases a median of five months post-thoracotomy (range one to six months). Two "biopsy only" patients were tumor free at 34+ and 56+ months. Local recurrence was observed in six of 12 resected patients, while six patients experienced only extrathoracic metastases. Median time to recurrence for resected patients was also five months. Four resected patients experienced late recurrence 16 to 36 months postoperatively and were alive with tumor at 29+ to 42+ months. Two resected patients were tumor-free at 13+ and 37+ months. Post-chemotherapy surgical resection was feasible in limited-stage patients and improved local control of disease.

Antineoplastic Agents↗
PubMed1987

Favorable prognosis of brain metastases in small cell lung cancer.

Brain metastases are found at diagnosis in 10% of patients with small cell lung cancer. To clarify the effect of central nervous system metastases on prognosis, the records of 429 patients with small cell lung cancer were reviewed. Forty-three patients (10%) presented with brain metastases. In 18 patients the brain was the only site of metastatic disease, whereas the remaining 25 patients had at least one additional metastatic site. Forty-one of forty-three patients were treated with combination chemotherapy and cranial radiotherapy. Systemic response rates were similar for both groups. Twenty-seven patients underwent repeat central nervous system staging: 19 (70%) had a complete response, 4 (15%) a partial response, and 4 (15%) no response. Median survival of patients with only one site of metastatic disease was 11 months; patients with additional sites lived 5 months (p = 0.153). Survival in patients with only one site is similar to that in patients with limited disease (11 compared with 13 months; p = 0.074).

Aged↗
PubMed1987

Human trabecular meshwork organ culture. A new method.

A new method has been developed for organ culture of human trabecular meshwork. Human eyebank eyes are sectioned at the equator and lens and vitreous are removed. The anterior segments are placed in a modified culture dish, cornea side up, and then sealed in place. Culture media (Dulbecco's modified Eagle media) are perfused through a cannula built into the bottom of the dish. The sealed system forces media to flow through the trabecular meshwork, Schlemm's canal, and exit through the normal limbal pathways. Intraocular pressure can be maintained at normal (or elevated) levels throughout the culture period. Corneal clarity is maintained. Trabecular cells remain in normal position on trabecular beams and maintain many of their usual morphologic characteristics. Cultures appear to be viable for up to 4 weeks. This technique should allow study of intact human trabecular meshwork in a controlled experimental fashion.

Aged↗
PubMed1986

Treatment of metastatic adrenal cortical carcinoma with cisplatin and etoposide (VP-16).

Two patients with metastatic adrenal cortical carcinoma were treated with cisplatin and etoposide. Both achieved a partial remission after only one cycle. One patient had a "nonfunctioning" tumor that had previously regressed on mitotane whereas the second patient presented with classical Cushing's syndrome. Although the latter patient's urinary 17-ketosteroids normalized while receiving mitotane, the tumor itself failed to regress objectively. Cisplatin plus etoposide appears to be an active combination for the treatment of metastatic adrenal cortical carcinoma.

Adrenal Cortex Neoplasms↗
PubMed1986

Breast cancer with skeletal metastases at initial diagnosis. Distinctive clinical characteristics and favorable prognosis.

Fifteen patients with breast cancer who had skeletal metastases already present at the time the primary breast lesion was detected, were retrospectively identified. The majority were postmenopausal, estrogen receptor-positive, and had large (often neglected) primary lesions. Eleven patients were asymptomatic with respect to their skeletal metastases, although bone scans and bone roentgenograms revealed multiple areas of involvement in all patients. The median survival from the time of diagnosis was 33 months (range, 1-74 months); the 5-year actuarial survival was 45%. Systemic therapy with hormones or chemotherapy was effective in producing subjective responses; radiotherapy to painful bony areas was also an effective palliative treatment. Median survival in this group of patients was significantly improved when compared to our breast cancer patients who had extraskeletal metastases at initial diagnosis (33 versus 9 months, respectively), and to previously reported series of breast cancer patients with metastases at initial diagnosis. Since patients with Stage IV breast cancer and metastases limited to the skeleton often have prolonged survival, complications from bone metastases (e.g. pathologic fracture, epidural spinal cord compression) and other intercurrent illnesses should be managed aggressively.

Actuarial Analysis↗
PubMed1986

Corneal changes during pilocarpine gel therapy.

Fifteen of 53 patients (28%) receiving long-term pilocarpine gel therapy were noted to have a subtle, diffuse superficial corneal haze. Results of a masked examination of patients using pilocarpine gel vs pilocarpine eyedrops and the finding of the haze unilaterally in patients using the gel unilaterally suggested that the haze is related to the pilocarpine gel. In most patients the haze persisted for two years after gel treatment was discontinued; the haze disappeared in two patients. Although patients remain asymptomatic with unaltered visual acuities, the long-term effect of this corneal change is unknown.

Conjunctiva↗
PubMed1986

Metastatic breast cancer confined to the skeletal system. An indolent disease.

The records of 86 patients with metastatic breast cancer confined to the skeletal system were retrospectively reviewed to evaluate the clinical impression that this subset of patients with metastatic breast cancer has a favorable prognosis. The median survival for this group of patients was 48 months, compared with a median survival of 17 months in patients with breast cancer metastatic to other sites (p less than 0.01). Systemic treatment with either hormonal therapy or chemotherapy was highly effective in these patients; 56 of 64 (87 percent) showed response to the first hormonal therapy received (median, 10 months; range, four to 54 months), and 43 of 46 (93 percent) showed response to initial chemotherapy (median, 11 months; range, six to 22 months). Most patients received several therapeutic modalities sequentially; sequential responses to hormonal therapy were frequent. Orthopedic complications were common (pathologic fracture in 18; epidural spinal cord compression in 13) and occurred a median of 24 months after documentation of bone metastasis. Prolonged survival was common after these complications (median, 18 months; range, two to 48 months). The presence of metastatic disease at the time of diagnosis and premenopausal status were not adverse prognostic factors. Metastases often remained localized to the skeleton; however, appearance of extraskeletal metastasis was associated with short subsequent survival (median, nine months). Metastatic breast cancer confined to the skeletal system is a common entity that can be defined clinically, is highly responsive to treatment, and is frequently associated with prolonged survival.

Adult↗
PubMed1986

Acute nonlymphocytic leukemia after treatment of small cell lung cancer.

From 1977 to 1982, 377 patients with small cell lung cancer were treated at Vanderbilt University Medical Center. All patients received combination chemotherapy consisting of cyclophosphamide, doxorubicin, and vincristine (CAV) with or without methotrexate, etoposide, and/or hexamethylmelamine. Thoracic and/or prophylactic cranial irradiation was administered to 159 (42 percent) and 192 (51 percent) patients, respectively. Acute nonlymphocytic leukemia was observed in two patients at 22 and 81 months from the start of therapy. The relative risk of leukemia was 154 (95 percent confidence limit, 38 to 293). A Kaplan-Meier estimate of the cumulative probability of leukemia was 1.9 +/- 1.4 percent seven years after the start of treatment. The relative risk of leukemia is significantly increased in this group of patients (p less than 0.0001). Acute nonlymphocytic leukemia is a long-term complication of small cell lung cancer therapy.

Adult↗
PubMed1986

Cloning a cDNA for Drosophila melanogaster urate oxidase.

A cDNA library from third-instar larval Malpighian tubules of Drosophila melanogaster was constructed and screened for urate oxidase (UO) clones by hybridization selection. The coding sequence for UO was mapped by in situ hybridization to position 28C on the left arm of chromosome 2. The UO activity in Drosophila shows a complex developmental profile. A UO cDNA was used as a probe of Northern blots of poly(A) + RNA from various stages of development. The data show that there is a direct correlation between the transcriptional activity of the UO locus as evidenced by the quantitative changes of UO mRNA and the levels of UO activity and protein during development.

Animals↗
PubMed1986

Superposition models of the discharge patterns of units in the lower auditory system.

Superposition of point processes has often been suggested as an abstract model for the generation of neural discharge patterns due to its simplicity (input spike trains are simply merged and then retransmitted by the model neuron). The properties of the superposition of two renewal processes are examined in relation to the properties of its components. A satisfactory condition is found so that the superposition of two renewal processes possesses negative serial dependence of intervent intervals. However, the imposition of a dead time of approximately the same duration as that of the components on their superposition process is shown to remove much of this dependence. Thus, the adequacy of the simple superposition of renewal processes as a model for discharge patterns from regions that are typified by negative serial dependence (such as the lateral superior olive) may be limited, but may suffice for the discharges of primary-like units.

Animals↗
PubMed1986

Application of a point process model to responses of cat lateral superior olive units to ipsilateral tones.

A general point process theory is developed to describe discharges recorded from lateral superior olivary units of the cat responding to ipsilaterally presented tone bursts and continuous tones. Statistical analysis of the stationary portion of the sequence of interspike intervals demonstrated that, for most units, the duration of each interval is statistically dependent only on the duration of the previous interval. A specific point process model is derived based on this analysis to describe the measured serial dependence as well as the deadtimes observed in interval histograms. The statistical dependence is well described as a shift of the interspike interval distribution, the shift depending on the duration of the previous interval. This model is then used to simulate the initial chopping in the tone burst responses. It is concluded that chopping responses and serial dependence do not result from properties of the unit's inputs; rather, they are consequences of the inherent characteristics of the unit.

Animals↗