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Biomedical subjects

D Solomon

Publications and source records attributed to D Solomon.

At least 109 records · Page 6Linked to original sources
PubMed1989

Comparison of insulin secretory patterns in obese nondiabetic LA/N-cp and obese diabetic SHR/N-cp rats. Role of hyperglycemia.

Obese diabetic SHR/N-(cp/cp) rats are a genetic model for non-insulin-dependent diabetes mellitus. When SHR/N-cp rats are overtly diabetic, they are hyperinsulinemic and hyperglycemic in the fed state when consuming commercial chow or semipurified high-carbohydrate diets. Obese SHR/N-cp rats were hyperinsulinemic by 4 wk of age, although hyperglycemia did not appear until 3-4 wk later and was exacerbated by a high-sucrose diet (mean +/- SE 1488 +/- 238 microU/ml insulin and 425 +/- 51 mg/dl glucose). The control SHR/N-cp rats (+/?) on the sucrose diet remained lean and normoglycemic. The obese diabetic SHR/N-cp rats showed three alterations in pancreas perfusion data (not present in control rats): 1) paradoxically high insulin secretion at low glucose levels (2.5 mM), 2) secretion of insulin in response to arginine (10 mM) in the absence of glucose, and 3) impaired response of insulin secretion to high glucose (16.7 mM). To determine whether hyperglycemia was responsible for the abnormalities of insulin secretion, perfusion studies were conducted in obese nondiabetic LA/N-cp rats and compared with the SHR/N-cp rats. The obese LA/N-cp rats resembled the corpulent SHR/N-cp rats in every way, except that they were normoglycemic on the sucrose diet. The obese LA/N-cp rats had two of the three alterations in insulin secretion shown by obese SHR/N-cp rats, lacking only the impaired response to high glucose, suggesting that hyperglycemia was required for that defect to occur.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Incidence of venous air embolism during cesarean section is unchanged by the use of a 5 to 10 degree head-up tilt.

One hundred healthy parturients were divided at random into two demographically similar groups and were positioned for cesarean section either horizontally or flexed 5 to 10 degrees head up, with a 15 degrees lateral tilt. A Doppler ultrasound transducer was positioned over the fourth intercostal space parasternally. Initially, two patients received spinal, three general, and 95 epidural anesthesia. Two patients subsequently needed general for failed epidural anesthesia. Changes in Doppler heart tones (greater than 15 sec duration) indicative of venous air embolism (VAE) were identified 15 times in 11 patients--seven in supine and four in head-up patients (no statistically significant difference). Six awake patients (three horizontal, three head-up) developed chest tightness or pain during surgery, but only one episode correlated with VAE. No patient developed breathlessness. Moderate hypotension (greater than 10% decrease in systolic arterial pressure [SAP]) occurred in seven of 11 (63.6%) patients with, and in 26 (29.2%) of 89 patients without, VAE (P less than 0.001). More severe hypotension (SAP less than 90 mm Hg) due to bleeding occurred once. We conclude that a modest (5-10 degrees) head-up position does not influence the occurrence of VAE in patients having cesarean section. An 11% incidence of clinically insignificant VAE, although low, is still worrisome, as even small air bubbles in the circulation are potentially harmful, especially if the foramen ovale is patent. VAE during cesarean section should be anticipated and the anesthetic management planned accordingly.

Adult↗
PubMed1989

Increasing the accuracy of fine-needle biopsy for thyroid nodules.

Fine-needle biopsy (FNB) is a valuable technique to use in the evaluation of thyroid nodules; however, false-negative and false-positive results do occur. At Sinai Hospital of Detroit (SHD) (Mich), a criterion was established for adequacy of an FNB specimen (ie, at least six clusters of benign cells on each of two slides prepared from separate aspirations) in an attempt to reduce the rate of false-negative diagnoses attributable to inadequate sampling. To evaluate the SHD criterion, 20 "problem" cases were selected from the SHD files and were reviewed by pathologists from three other institutions in a blind study. A total of 80 diagnoses were rendered (four institutions each reviewing 20 cases). Seven false-negative diagnoses were rendered, three of which were made in cases that did not meet the SHD criterion for adequacy. An additional three false-negative diagnoses on inadequate FNB specimens were made by a physician who asked not to be identified. Implementation of the SHD criterion may reduce the frequency of false-negative diagnoses. A separate study was undertaken to determine the number of FNB aspirations necessary to obtain satisfactory specimens. One hundred adequate FNB specimens from SHD files were reviewed. In 77% of cases the first two to four aspirations were adequate, but 23% of the time six to eight aspirations were necessary to obtain adequate material.

Adenocarcinoma↗
PubMed1988

Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. A preliminary report.

Lymphocytes extracted from freshly resected melanomas can be expanded in vitro and can often mediate specific lysis of autologous tumor cells but not allogeneic tumor or autologous normal cells. We treated 20 patients with metastatic melanoma by means of adoptive transfer of these tumor-infiltrating lymphocytes and interleukin-2, after the patients had received a single intravenous dose of cyclophosphamide. Objective regression of the cancer was observed in 9 of 15 patients (60 percent) who had not previously been treated with interleukin-2 and in 2 of 5 patients (40 percent) in whom previous therapy with interleukin-2 had failed. Regression of cancer occurred in the lungs, liver, bone, skin, and subcutaneous sites and lasted from 2 to more than 13 months. Toxic effects of interleukin-2 occurred, although the treatment course was short (five days); these side effects were reversible. It appears that in patients with metastatic melanoma, this experimental treatment regimen can produce higher response rates than those achieved with interleukin-2 administered alone or with lymphokine-activated killer cells. It is too early to determine whether this new form of immunotherapy can improve survival, but further trials seem warranted.

Adult↗
PubMed1988

Renal pathology in von Hippel-Lindau disease.

Von Hippel-Lindau disease, a rare autosomal disorder, is associated with multiple lesions, including a high incidence of renal lesions and CNS hemangioblastomas. Renal lesions have traditionally been classified as either benign cysts or solid renal cell carcinomas with or without cystic degeneration. We examined seven kidney specimens from four patients with von Hippel-Lindau disease. We found that renal cysts form a histopathologic continuum ranging from benign cysts (with one to two cell layers of bland epithelium), atypical cysts (demonstrating epithelial hyperplasia with or without mild cytologic atypia), to malignant cysts harboring renal cell carcinoma. The presence of atypia or foci of carcinoma does not correlate with cyst size. Lesions that appear radiologically or grossly solid range from conventional solid renal cell carcinoma, sometimes evidencing cystic degeneration, to lesions that are predominantly hyalinized, fibrotic nodules. In contrast to simple cysts occurring in the general population, which are virtually always benign, renal cysts in patients with von Hippel-Lindau disease may contain occult carcinoma. Radiologic evaluation, visual inspection at surgery, and even frozen section analysis of cyst lesions cannot be relied on to detect small foci of carcinoma. The spectrum of pathologic changes and the multicentricity of the renal lesions in von Hippel-Lindau disease complicate the radiologic evaluation and surgical management of these patients.

Adult↗
PubMed1988

Residual abdominal masses in aggressive non-Hodgkin's lymphoma after combination chemotherapy: significance and management.

When patients with aggressive lymphoma present with intraabdominal disease, a stable residual mass is frequently detected radiographically at the time of the clinical complete remission. To discern the optimal management for this clinical problem, we reviewed 241 patients with aggressive lymphoma treated at the National Cancer Institute (NCI) from 1977 to 1986. Seventy-two/241 patients (30%) had an abdominal mass at diagnosis and 29/72 (40%) were left with a radiographically detectable residual mass at clinical complete remission. The likelihood of a residual mass was much higher for patients with bulky disease (P2 less than .0003) (two-tailed test [P2]). Twenty-nine patients had radiologically stable residual masses after therapy, and of 22 (76%) with pathologic evaluations, 21 had negative specimens (95%) and one was positive (5%). None of the patients with negative pathologic evaluation has relapsed in the abdominal site (median follow-up, 31 months). Seven patients were observed clinically without laparotomy: five are alive, without evidence of disease, at 2 to 9 years; two relapsed with disseminated disease within 2 months of chemotherapy. Initial tumor size and size of the residual mass did not correlate with residual disease, since residual masses identified by radiographic examination did not usually harbor viable lymphoma cells. Aspiration cytology was negative for residual tumor in 15/16 cases. One negative result was not confirmed at laparotomy, presumably due to sampling error. The one positive aspiration was followed by a negative laparotomy, possibly due to subsequent tumor necrosis. Restaging laparotomy has a low yield. In most patients with aggressive lymphoma who have otherwise completely responded to carefully administered full-dose combination chemotherapy, stable residual abdominal masses can be closely followed clinically without surgical exploration.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Immunotherapy of patients with advanced cancer using tumor-infiltrating lymphocytes and recombinant interleukin-2: a pilot study.

Clinical investigations using the adoptive transfer of lymphokine-activated killer (LAK) cells and recombinant interleukin-2 (rIL-2) to treat patients with advanced cancer have yielded encouraging results. We have thus sought ways to enhance the effectiveness of adoptive immunotherapy while minimizing its toxic side effects. Murine experiments have identified tumor-infiltrating lymphocytes (TIL) as killer cells more effective than LAK cells and less dependent on adjunctive systemically administered IL-2 to mediate antitumor effects. Accordingly, we performed a pilot protocol to investigate the feasibility and practicality of administering IL-2-expanded TIL to humans with metastatic cancers. Twelve patients, including six with melanoma, four with renal cell carcinoma, one with breast carcinoma, and one with colon carcinoma, were treated with varying doses and combinations of TIL (8.0 X 10(9) to 2.3 X 10(11) cells per patient), IL-2 (10,000 to 100,000 U/kg three times daily to dose-limiting toxicity), and cyclophosphamide (CPM) (up to 50 mg/kg). Two partial responses (PR) to therapy were observed: pulmonary and mediastinal masses regressed in a patient with melanoma, and a lymph node mass regressed in a patient with renal cell carcinoma. One additional patient with breast cancer experienced a partial regression of disease in lymph nodal and cutaneous sites with complete elimination of malignant cells from a pleural effusion, although cutaneous disease recurred at 4 weeks. The toxicities of therapy were similar to those ascribed to IL-2; no toxic effects were directly attributable to TIL infusions. In five of six melanoma patients, TIL demonstrated lytic activity specific for the autologous tumor target in short-term chromium-release assays, distinct from the nonspecific lytic activity characteristic of LAK cells. This study represents an initial attempt to identify and use lymphocyte subsets with enhanced tumoricidal capacity in the adoptive immunotherapy of human malignancies.

Adult↗
PubMed1987

Expansion of human tumor infiltrating lymphocytes for use in immunotherapy trials.

The potential utility of tumor-infiltrating lymphocytes (TIL) in the adoptive immunotherapy of human tumors has been suggested by murine experiments showing these cells to be 50-100 times more powerful than LAK cells in treating advanced metastatic disease. A method for the large-scale expansion of human TIL for the use of these cells in clinical trials is described in this report. TIL were successfully expanded on an experimental scale from 24 of 25 consecutive human tumors, including six melanomas, ten sarcomas, and eight adenocarcinomas. Tumors were digested enzymatically to yield single cell suspensions which were cultured in RPMI 1640 medium with 10% human serum and 1000 U/ml recombinant interleukin-2. Lymphocytes constituted from 3% to 74% of single cell tumor suspensions, and expanded from 2.9-fold to 9.1 X 10(8)-fold over a culture period ranging from 14 to 100 days. Nine of 24 TIL cultures lysed fresh autologous tumor targets in 4 h chromium release assays. Cell surface phenotyping identified cultured TIL as activated cytotoxic/suppressor T cells. Subsequently, large-scale expansion of TIL was successful in generating more than 10(10) lymphocytes in five of eight consecutive cases. Clinical trials employing the adoptive transfer of expanded TIL to patients with metastatic disease have begun.

Cells, Cultured↗
PubMed1987

Solid and papillary epithelial neoplasm of the pancreas. An ultrastructural and immunocytochemical study of six cases.

Solid and papillary epithelial neoplasms of the pancreas from six female patients were studied using immunohistochemistry and electron microscopy to define better their histogenesis. The tumors ranged in diameter from 5 to 15 cm (average: 9 cm), and, on cross section, most had areas of hemorrhage and necrosis, sometimes extensive. Microscopically, there was a solid and pseudopapillary pattern, with tumor cells typically having ovoid nuclei with delicate folding and indistinct nucleoli. Of note were the following: a relatively low mitotic rate (range: 0-6/20 hpf), the presence of hyaline globules (four of six cases), and collections of foam cells (three of six cases). Staining for cytoplasmic argyrophil granules was negative in each case. Ultrastructurally, the solid and papillary epithelial neoplasms of the pancreas showed evidence of acinar or ductular differentiation. Two contained zymogen granules, one had intermediate filaments (probably keratin), and three had abundant rough endoplasmic reticulum and mitochondria. Immunostaining was positive for chymotrypsin (six of six cases), trypsin (four of six), and amylase (three of six). None was positive for alpha-1-antitrypsin, neuron-specific enolase, pancreatic polypeptide, gastrin, glucagon, somatostatin, or insulin. The findings support an origin from exocrine pancreas, and follow-up indicates a low rate of malignancy, with local recurrence in two of the six patients.

Adolescent↗
PubMed1985

Malignant transformation in non-irradiated recurrent respiratory papillomatosis.

The clinical, radiographic and post mortem findings occurring in a 6-year-old female with a four-year history of recurrent respiratory papillomatosis (RRP) are described. At autopsy, there were two separate foci of malignant transformation (malignant degeneration) in the bronchioloalveolar papillomata. This patient is the youngest in whom such changes have been described. Malignant transformation is a rare occurrence and is usually seen in older patients with longstanding papillomatosis, therapeutic irradiation, or a history of smoking. Pulmonary spread represents the majority of cases with "spontaneous" malignant transformation.

Age Factors↗
PubMed1985

Multifocal disease in the upper genital canal.

Multifocal disease, both benign and malignant, is seen commonly in the lower genital canal. Conversely, malignancies developing concomitantly in the uterus and ovary are frequently diagnosed as metastatic disease. In this series of 54 cases, the overall five-year survival was 72%, and 90% when the lesions were limited to the uterus and ovary, demonstrating that these lesions are multifocal and not metastatic. Furthermore, the frequency with which endometriosis is found in association with these malignancies dictates that the adjunctive therapy should probably be progesterone in most instances.

Adenocarcinoma↗
PubMed1983

Prevention of experimental allergic encephalitis with in vivo administration of anti I-A antibody. Decreased accumulation of radiolabelled lymph node cells in the central nervous system.

Experimental allergic encephalitis (EAE) can be prevented with the in vivo administration of monoclonal anti I-A antibody. A radiometric assay was developed to measure the accumulation of lymphocytes in the central nervous system of EAE animals. A direct correlation was observed between severity of clinical disease and the amount of radiolabelled lymph node cells (LNC) in the central nervous system. Injection of anti I-A antibody in vivo prevented clinical EAE and decreased the accumulation of radiolabelled LNC in spinal cord after immunization with mouse spinal cord homogenate and adjuvants.

Animals↗
PubMed1982

Chemical properties of water-soluble porphyrins 3. The reaction of superoxide radicals with some metalloporphyrins.

The catalytic efficiency of some water soluble metalloporphyrins upon the disproportionation of the superoxide radicals has been determined by observing the rate of decay of the radical at 254 nm. The Fe(III), Mn(III), Co(III), Ni(II), Cu(II) and Zn(II) derivatives of tetrakis-(4-N-methylpyridyl) porphyrin (TMPyP), tetra(4-N,N,N-trimethylanilinium) porphyrin (TAP), and tetra(4-sulphonatophenyl) porphyrin (TPPS4) were studied. The order of catalytic efficiency found was Fe(III)TMPyP much greater than Mn(III)TMPyP greater than Co(III)TMPyP approximately equal to Mn(TAP) greater than Fe(III)TPPS4. Other metalloporphyrins did not show catalytic activity. Reduction potentials of the catalytically active metalloporphyrins determined from cyclic voltamograms indicate the importance of having a second energetically accessible oxidation state available to the metal ion for catalysis. The catalytic action of the above metalloporphyrins is discussed in terms of inner and outer-sphere mechanisms. It is suggested that with the exception of Fe(III)TMPyP which reacts via an inner-sphere mechanism, the others are governed by an outer-sphere mechanism.

Cobalt↗
PubMed1982

Identification of T cell subsets and B lymphocytes in mouse brain experimental allergic encephalitis lesions.

Tissue section immunoperoxidase staining, employing monoclonal antibodies specific for T cell antigens (Lyt-1, Lyt-2) and B cells (B220), was used to study the brains of mice with experimental allergic encephalitis. Cells bearing phenotypes characteristic of both helper (Lyt-1+2-) and cytotoxic/suppressor (or precursor) (Lyt-2+) T cells, as well as B cells, are present in the perivascular cuffs in brains of EAE mice during active disease and the recovery phase. Lyt-1+ cells comprise 49% of the inflammatory cell population, and Lyt-2+ and B220+ cells are found at frequencies of 10% and 12%, respectively.

Animals↗