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Biomedical subjects

D H Johnson

Publications and source records attributed to D H Johnson.

At least 253 records · Page 14Linked to original sources
PubMed1989

Phase I clinical study of N-[(4-chlorophenyl)amino]carbonyl-2,3-dihydro-1H-indene-5-sulfonamide (LY186641).

Between February 1987 and July 1988, 45 patients with advanced refractory cancer were treated with LY186641, a diarylsulfonylurea that has shown a broad spectrum of activity in preclinical testing. Patients received a weekly p.o. dose of LY186641 for 6 consecutive weeks; responding and stable patients continued weekly therapy until progression occurred. Using a standard phase I study design, the first three patients received LY186641 at 30 mg/m2 week; the dose was escalated in subsequent patients until dose-limiting toxicity occurred. Methemoglobinemia was the major toxicity observed and was dose related. Methemoglobin levels peaked approximately 24 h after LY186641 was administered and fell to low levels after 48 h. Six patients developed fatigue, cyanosis, and dyspnea associated with serum methemoglobinemia levels of greater than 20%; four of these patients were subsequently removed from the study. Hemolytic anemia was also observed but was clinically significant in only 10 patients. Other side effects were mild and infrequent. The maximum tolerated dose of LY186641, when given at this schedule, was 2550 mg/m2/week. No objective tumor responses were observed.

Antineoplastic Agents↗
PubMed1989

Does pigmentation affect the trabecular meshwork?

Pigment has been associated with glaucoma in pigment dispersion syndrome and in intraocular lens-associated pigment dispersion. Human eyes with segmental pigmentation of the trabecular meshwork may provide a controlled model to study the effects of pigment on the meshwork. Nine normal human eye bank eyes with segmental pigmentation of the trabecular meshwork were examined for pigment-associated differences in trabecular cellularity or morphology. Cellularity was examined with four methods: cells per histologic section, cells per length of tissue, cells per overall area, and cells per solid tissue. The simplest method, cells per histologic section, gave results equivalent to the other methods. No differences in cellularity or morphology were found between pigmented and nonpigmented areas.

Adult↗
PubMed1989

Difficult tracheal extubation.

We describe a case of nasotracheal tube fixation with a screw. A second case is described in which a broken drill bit was found to impinge on the wall but not penetrate into the lumen of a nasotracheal tube. Possible sequelae of this complication include airway leak, aspiration, tube obstruction, and trauma from attempts at forceful extubation. We recommend the routine intraoperative testing for tracheal tube movement and routine fibreoptic bronchoscopy through the tube when blind surgical procedures occur in the vicinity of a tracheal tube.

Adolescent↗
PubMed1989

The effect of organ culture on human trabecular meshwork.

The effect of organ culture on the trabecular meshwork was studied in a series of human eyes using a perfusion culture system. One eye of a pair was cultured while the fellow eye was immediately fixed in glutaraldehyde. Culture periods ranged from 2 to 28 days, during which a mean intraocular pressure of 27 mmHg +/- 15 was maintained. The perfused culture medium appeared to leave the eye via Schlemm's canal and collector channels, mimicking the in vivo situation. The trabecular meshwork was well maintained with this system in 21 of 25 eyes. Cells remained in position on trabecular lamellae, cellular organelles usually remained normal, and the lamellae remained intact. Culture-induced changes were noted, with some cells developing intracytoplasmic lipid vacuoles and other cells developing swollen mitochondria. In addition, scattered focal cell necrosis was observed, most often in the uveal meshwork. Meshwork cellularity (nuclei:solid tissue) was determined with an image analysis system; there was an average cell loss of 20-40% in the cultured eyes as compared to their respective fellow control eyes. Overall, organ culture appears to maintain the human trabecular meshwork for at least 28 days, allowing controlled experimental studies to be performed.

Aged↗
PubMed1989

Congenital malformations and psychosocial development in children conceived by in vitro fertilization.

To determine whether in vitro fertilization (IVF) as a method of conception is associated with an increased risk for congenital malformations or developmental dysfunction, we performed a general physical examination for malformations, neurologic examination, developmental examination (Bayley Scales), echocardiography, electrocardiography, abdominal ultrasound study, and, when possible, cranial ultrasound examination on a cohort of 83 IVF children and 93 matched non-IVF children. Major malformations were found in two IVF and one non-IVF subject; the rates were not significantly different. The mean Mental Development Index scores for IVF subjects and the comparison group were 115 +/- 13 and 111 +/- 13, respectively (p = 0.12). The mean Psychomotor Development Index scores were 114 +/- 14 and 108 +/- 15 (p = 0.04). Based on these small numbers but extensive evaluation, we found no association between conception by IVF and an increased risk for congenital malformations. Likewise, children conceived by IVF showed no evidence of developmental delay. Their high average achievement on the Bayley tests probably resulted from the exceptional motivation of their parents ("wantedness") and their generally high socioeconomic status.

Child Development↗
PubMed1989

Primary lymphoma of the central nervous system. A report of 20 cases and a review of the literature.

Twenty patients with primary non-Hodgkin's lymphoma of the central nervous system (CNS) were seen at Vanderbilt and its affiliated hospitals between 1974 and 1986. Histologically, the most common subtypes were large, noncleaved cell lymphoma and immunoblastic lymphoma of B cells. However, multiple histologies were identified. Lesions most commonly involved the frontal lobes and/or deep nuclei. Positive cerebrospinal fluid cytology was rare at initial presentation. Seventeen patients were treated with surgical biopsy or resection followed by whole brain radiotherapy at a median dose of 5,000 cGy (range: 3,000-5,600 cGy). Seven patients have been followed for less than 12 months since diagnosis. Of the remaining patients, 7 (54%) survived at least 1 year. The extent of surgery performed, dose of radiotherapy administered, subclass of lymphoma diagnosed, or location(s) of involvement within the CNS did not influence survival. Treatment rarely caused a dramatic improvement in performance status despite objective signs of response. New treatment strategies are needed to improve the management of these tumors.

Adult↗
PubMed1989

Chemotherapy of advanced non-small-cell lung cancer: a randomized trial of three cis-platin-based chemotherapy regimens.

One hundred fifty-two patients with locally advanced or metastatic non-small-cell lung cancer were randomized to receive treatment with one of three cis-platin-containing chemotherapy regimens: vindesine/cis-platin, etoposide/cis-platin, or vindesine/etoposide/cis-platin. Following an 8-week induction course of treatment, patients were evaluated for response; responders continued to receive monthly chemotherapy. All patients were followed until death. Response rates for the three regimens were 10%, 6%, and 24%, respectively; the cis-platin/vindesine/etoposide regimen produced more responses than did either cis-platin/etoposide or cis-platin/vindesine (p less than 0.05). However, median survival was not improved with the three-drug regimen, and myelosuppression produced by this regimen was worse. The 20-week median survival for the entire group suggests that these treatments had no impact on survival. None of these regimens can be recommended for routine treatment of patients with advanced non-small-cell lung cancer. The addition of vindesine did not make a significant impact in response rate or overall survival in this study.

Actuarial Analysis↗
PubMed1989

Chronic daily administration of oral etoposide--a phase I trial.

In this phase I study, we administered etoposide (VP-16) orally for 21 consecutive days to patients with advanced refractory cancers. All patients had received previous chemotherapy, and 50% of patients had received more than one combination regimen. When given for 21 consecutive days, the maximum-tolerated dose of oral VP-16 was 50 mg/m2/d. Myelosuppression was the dose-limiting toxicity, and occurred between days 21 and 28. In most patients, blood counts had recovered sufficiently by day 35 to begin another 3-week course. WBC count nadirs of less than 1,000/microL occurred in four of 20 courses at this dose, and three patients required hospitalization for treatment of neutropenia and fever. Alopecia occurred in most patients; gastrointestinal (GI) and other toxicities were uncommon. Five of 16 patients with measurable tumor had partial responses of 3 to 4 months duration. Four of these five patients had malignancies that are usually unresponsive to VP-16 when administered by previously investigated schedules. This method of VP-16 administration is well tolerated, convenient, and may optimize antitumor efficacy by exploiting the schedule dependency of this drug. Phase II studies are necessary to define the level of activity of this schedule of VP-16.

Administration, Oral↗
PubMed1989

Combined small-cell and non-small-cell lung cancer.

Nine (2%) of 429 small-cell lung cancer (SCLC) patients seen at Vanderbilt University between 1977 and 1983 had a combined subtype SCLC at diagnosis (ie, small-cell carcinoma plus squamous cell or adenocarcinoma). Staging procedures and chemotherapy treatment were uniform for all 429 patients. The diagnosis of combined histology was established via bronchoscopy (six patients), needle aspiration biopsy (one), lymph node biopsy (one), and thoracotomy (one). The clinical characteristics of the combined subtype patients were similar to patients with other subtypes of SCLC (ie, there were no differences in median age, sex, performance status, and stage of disease). However, patients with a combined subtype histology had a higher incidence of peripheral lesions on chest x-ray (56% v 14%, P less than .001) and a lower median lactate dehydrogenase (LDH) (301 IU/L v 341 IU/L, P = .0002) at diagnosis. The overall response to chemotherapy (57% v 78; P = .5) and the median survival (8 months v 10 months; P = .4) of the combined subtype patients were similar to patients with other subtypes of SCLC. Two (22%) combined histology patients survived greater than or equal to 5 years. Both had had surgical resection in addition to chemotherapy. These data suggest that the combined subtype of SCLC is clinically similar to pure SCLCs and that surgery may play a prominent role in the management of these tumors. The possibility of a combined histology tumor should be considered in patients thought to have SCLC on the basis of limited biopsy material, such as a needle aspiration or bronchial biopsy, and when the primary lesion is peripherally located on chest x-ray.

Adenocarcinoma↗
PubMed1989

Trabecular meshwork recovery after phagocytic challenge.

The short and long term response of the trabecular meshwork to a phagocytic challenge and the response of the meshwork to different types of foreign particles was studied by injecting one eye of 25 adult cats with a phagocytic agent (zymosan, blood, or latex microspheres) while the fellow eye received a control solution. Eyes were examined histologically at various intervals from one day to five months after infusion. Active trabecular cell phagocytosis and changes in cell shape were found with all agents. The extent of these changes varied with the agent used. Zymosan caused marked changes and inflammation, with numerous macrophages found throughout the meshwork. Trabecular cell migration and cell loss occurred, although it was often difficult to distinguish macrophages from rounded trabecular cells. The meshwork eventually recovered from this inflammatory insult, as trabecular lamellae became less edematous and once again acquired a lining of trabecular cells. Blood and latex microspheres caused less disruption, with microspheres often found in otherwise normal appearing cells. Trabecular cellularity was quantitated after the blood and the zymosan infusions. No cell loss was observed after the blood infusion, while zymosan-infused eyes had an initial 15% cell loss (p less than .04) when compared with fellow control eyes. This zymosan-associated trabecular cell loss may have been due to phagocytosis, inflammation, or a combination of both. The cell loss had recovered by the end of 150 days (p less than .02), as trabecular cell numbers in experimental eyes became comparable to fellow control eyes.

Animals↗
PubMed1988

Late recurrences in long-term survivors of germ cell neoplasms.

Patients with germ cell neoplasms who are in complete remission 2 years after treatment have a very high probability of cure, and reports of recurrences occurring after 2 years are rare. Of 81 testicular cancer patients treated for advanced disease at Vanderbilt University between 1970 and 1985, five developed a recurrent or metachronous germinal tumor 58 to 195 months after the initial treatment. Only two of these patients had received prior cisplatin-based combination chemotherapy. Four patients had unfavorable prognostic features when tumor recurrence was diagnosed. All five patients responded to salvage chemotherapy, although there were only two complete responses. The extent of disease was a significant factor in predicting response to salvage therapy. The possible mechanisms of development of a late recurrence of germinal neoplasms include the following: (1) malignant degeneration of mature teratoma to germinal malignancy; (2) growth of an occult testicular tumor not eliminated by chemotherapy due to the presence of a blood-testicular barrier; (3) development of a second primary germ cell neoplasm; or (4) late relapse due to persistent microscopic viable tumor with an atypical less aggressive biologic behavior. "Cured" germ cell tumor patients need careful follow-up beyond 2 years. At a minimum, these patients should be seen annually. Patients found to have teratomas following cisplatin-based chemotherapy should probably undergo more frequent evaluations.

Adult↗
PubMed1988

Poorly differentiated neuroendocrine carcinoma of unknown primary site. A newly recognized clinicopathologic entity.

Twenty-nine patients with poorly differentiated neuroendocrine tumors of unknown primary site were seen at Vanderbilt Medical Center between May 1977 and February 1987. All patients had pathologic findings typical of neuroendocrine tumors by electron microscopy (22 patients), light microscopy (6 patients), or immunochemical staining (1 patient). Patient age ranged from 18 to 77 years; 21 were men and 8 were women; and 12 had no history of tobacco use. Seventeen patients had metastatic tumor at two or more locations. Common metastatic sites included the retroperitoneum, lymph nodes (particularly cervical), and mediastinum. In most patients, these neoplasms showed an aggressive biology, with rapid onset of symptoms and rapid growth of metastases. Major responses were seen in 18 of 25 patients who received combination chemotherapy; 6 patients achieved a complete response. Three patients remain disease-free more than 24 months after completing therapy. Four patients with single sites of disease received local therapy only; all remain disease-free 1 to 10 years after completion of therapy. In 4 patients, specific tumor types were eventually recognized: small cell lung cancer, 1; gastrointestinal carcinoid tumor, 2; and extragonadal germinal tumor with predominant neuroendocrine differentiation, 1. In the remaining 25 patients, no well-recognized type of neuroendocrine tumor was identified. Recognition of these tumors broadens the spectrum of neuroendocrine neoplasia, and also identifies a distinct subset of patients with poorly differentiated carcinoma of unknown primary site. Although optimal therapy remains undefined, these patients are usually responsive to combination chemotherapy, and long-term survival is attainable in a minority.

Adenocarcinoma↗
PubMed1988

Transatrial repair of double-chambered right ventricle.

Double-chambered right ventricles (DCRVCs) traditionally have been repaired via a right ventriculotomy. We describe the cases of 8 children (aged 7 months to 6 years; weight, 6.3 to 21.5 kg), who underwent repair of DCRV via a right atriotomy. Six patients had ventricular septal defects. Peak systolic gradients in the right ventricular outflow tract were 26 to 135 mm Hg. The QP/QS were 1.1 to 2.5. Cardiopulmonary bypass times were 52 to 89 min (mean, 65.5 min) with aortic cross-clamp times of 20 to 56 min (mean, 39 min). Mean intraoperative gradients following repair were 5.8 mm Hg. Three patients had transient postoperative atrioventricular block requiring temporary pacing. Two patients required minimal inotropic support (dopamine, 2.5 to 5 micrograms/kg/min). The children have all been asymptomatic after hospitalization with follow-up times of 5 months to 4.5 years. No patient requires cardiac medications or has significant, persistent dysrhythmias; however, 1 patient required reoperation. Transatrial repair of DCRV allows excellent operative anatomical visualization and should be considered as an alternative to the transventricular approach in patients with this congenital heart defect.

Cardiac Surgical Procedures↗
PubMed1988

The brown protein of Drosophila melanogaster is similar to the white protein and to components of active transport complexes.

The brown gene of Drosophila melanogaster is required for deposition of pteridine pigments in the compound eye and other tissues. We isolated a ca. 150-kilobase region including brown by microdissection and chromosome walking using cosmids. Among the cDNAs identified by hybridization to the cosmids, one class hybridized to a genomic region that is interrupted in two brown mutants, bw and In(2LR)CK, and to 2.8- and 3.0-kilobase poly(A)+ RNAs which are altered in the mutants. Nucleotide sequencing of these cDNAs revealed that the two transcripts differ as a consequence of alternative poly(A) addition and that both encode the same predicted protein of 675 amino acids. Searches of available databases for amino acid sequence similarities detected a striking overall similarity of this predicted protein to that of the D. melanogaster white gene. The N-terminal portion aligned with the HisP family of membrane-associated ATP-binding proteins, most of which are subunits of active transport complexes in bacteria, and to two regions of the multidrug resistance P-glycoprotein. The C-terminal portion showed a structural similarity to integral membrane components of the same complexes. Taken together with earlier biochemical evidence that brown and white gene products are necessary for uptake of a pteridine precursor and genetic evidence that brown and white proteins interact, our results are consistent with suggestions that these proteins are subunits of a pteridine precursor permease.

ATP-Binding Cassette Transporters↗
PubMed1988

Cisplatin plus etoposide consolidation following cyclophosphamide, doxorubicin, and vincristine in limited small-cell lung cancer.

From June 1982 through October 1985, the Southeastern Cancer Study Group randomized patients with limited small-cell lung cancer (SCLC) to cyclophosphamide plus doxorubicin (Adriamycin, Adria Laboratories, Columbus, OH) plus vincristine (CAV) for six cycles v CAV plus concomitant thoracic irradiation as induction therapy. Patients achieving either a complete or partial response and remaining in remission after completion of induction therapy were subsequently randomized to consolidation chemotherapy consisting of cisplatin 20 mg/m2 X 4 plus etoposide (VP-16) 100 mg/m2 X 4 every 4 weeks for two courses v no further therapy. There were 160 patients entered on the consolidation phase and 148 were fully evaluable. The median survival for patients randomized to cisplatin plus VP-16 (PVP16) from start of CAV chemotherapy was 97.7 weeks, compared with 68 weeks for the no-consolidation arm (P = .0094). PVP16 consolidation also significantly increased the duration of remission, with median durations of 49 weeks v 28 weeks (P = .0008). The median durations for partial remission were 41 weeks v 23 weeks (P = .013), and for complete remission, 52 weeks v 30.5 weeks (P = .0091). Furthermore, 18 patients on PVP16 consolidation remain in a continuous complete remission for 12+ months and 13 of these are continuously disease free 2+ years. Eight patients randomized to no consolidation remain in a continuous complete remission, with only four patients disease free 2+ years. PVP16 consolidation has significantly improved the duration of remission and overall survival and appears capable of improving the cure rate in limited SCLC.

Adult↗
PubMed1988

Non-Hodgkin's lymphoma of the gastrointestinal tract: an analysis of clinical and pathologic features affecting outcome.

Clinical and histopathologic data from 87 patients with primary non-Hodgkin's lymphoma of the gastrointestinal (GI) tract diagnosed between 1974 and 1984 were reviewed. B-cell lymphomas of intermediate- or high-grade histology constituted 78% of lesions. Stage of disease varied with histologic grade, with a preponderance of advanced disease (stages IIIE and IV) in patients with low-grade lymphoma (15 of 21) (71%), compared with higher grade lesions (38%, P = .01). Among patients with nonlocalized (stages IIE through IV) lymphoma of intermediate- or high-grade histology, surgical resection of the primary focus afforded a higher rate of complete remission (CR) (70% v 50%) and sustained CR (61% v 21%, P = .04) after cytotoxic therapy compared with the nonresected cohort. The median survival in the resected group was 51 months + compared with 13 months in the nonresected patients (P = .012). Differences in outcome were attributable to a high risk of treatment-related complications (perforation and/or hemorrhage) (43% v 0%, P = .001) and local relapse (29% v 4%, P = .05) in nonresected individuals. Life-threatening local complications were not observed in patients with low-grade lymphoma managed solely with medical therapy. Histologic findings from surgically staged patients identified presence of extravisceral disease and intermediate- or high-grade tumor histology as features predictive of transmural invasion, enabling potential identification of patients who might be optimally managed by resection of the primary GI focus before initiation of cytotoxic therapy.

Adolescent↗