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Biomedical subjects

G L Davis

Publications and source records attributed to G L Davis.

At least 73 records · Page 4Linked to original sources
PubMed1996

Breakdown of blood pressure and body fluid homeostasis in heart transplant recipients.

OBJECTIVES: This study was designed to investigate disturbances in arterial blood pressure and body fluid homeostasis in stable heart transplant recipients. BACKGROUND: Hypertension and fluid retention frequently complicate heart transplantation. METHODS: Blood pressure, renal and endocrine responses to acute volume expansion were compared in 10 heart transplant recipients (57 +/- 9 years old [mean +/- SD]) 20 +/- 5 months after transplantation, 6 liver transplant recipients receiving similar doses of cyclosporine (cyclosporine control group) and 7 normal volunteers (normal control subjects). After 3 days of a constant diet containing 87 mEq/24 h of sodium, 0.154 mol/liter saline was infused at 8 ml/kg per h for 4 h. Blood pressure and plasma vasopressin, angiotensin II, aldosterone, atrial natiuretic peptide and renin activity levels were determined before and at 30, 60, 120 and 240 min during the infusion. Urine was collected at 2 and 4 h. Blood pressure, fluid balance hormones and renal function were monitored for 48 h after the infusion. RESULTS: Blood pressure did not change in the two control groups but increased in the heart transplant recipients (+15 +/- 8/8 +/- 5 mm Hg) and remained elevated for 48 h (p < or = 0.05). Urine flow and urinary sodium excretion increased abruptly in the control groups sufficient to account for elimination of 86 +/- 9% of the sodium load by 48 h; the increases were blunted (p < or = 0.05) and delayed in the heart transplant recipients, resulting in elimination of only 51 +/- 13% of the sodium load. Saline infusion suppressed vasopressin, renin activity, angiotensin II and aldosterone in the two control groups (p < or = 0.05) but not in the heart transplant recipients. Heart transplant recipients had elevated atrial natriuretic peptide levels at baseline (p < or = 0.05), but relative increases during the infusion were similar to those in both control groups. CONCLUSIONS: Blood pressure in heart transplant recipients is salt sensitive. These patients have a blunted diuretic and natriuretic response to volume expansion that may be mediated by a failure to reflexly suppress fluid regulatory hormones. These defects in blood pressure and fluid homeostasis were not seen in liver transplant recipients receiving cyclosporine and therefore cannot be attributed to cyclosporine alone. Abnormal cardiorenal neuroendocrine reflexes, secondary to cardiac denervation, may contribute to salt-sensitive hypertension and fluid retention in heart transplant recipients.

Angiotensin II↗
PubMed1996

Interferon therapy for chronic hepatitis C.

Interferon alone is currently the treatment of choice for chronic hepatitis C. The optimal treatment regimen continues to be defined and refined by clinical studies. The variability of the response to interferon seems to be influenced by several factors, including liver histology, viral genotype, level of viraemia, number of predominant quasispecies, and perhaps the type of interferon and treatment regimen. It is therefore quite likely that, in the future, treatment regimens will be tailored to the individual patient in order to maximize the likelihood of a beneficial outcome. It is also likely that the increasing availability of sensitive, quantitative, and affordable assays of hepatitis C viral levels will allow physicians to assess treatment response quite differently from the way we do so today. This will change our philosophy such that we will begin to view and treat chronic hepatitis C as an infection, instead of simply as a liver disease.

Antiviral Agents↗
PubMed1996

Malignant melanoma arising in mature ovarian cystic teratoma (dermoid cyst). Report of two cases and literature analysis.

Malignant melanoma may originate from melanocytes in ovarian cystic teratomas (dermoid cysts). Two cases are reported here and an additional 17 cases are found in a literature review covering 1903-1995. The review also found cases of benign and malignant melanotic ovarian lesion unassociated with dermoid cyst, including four melanomas, three cases of benign nevus, five cases of benign melanosis, and four cases of benign and malignant retinal anlage tumors. The extremely rare primary ovarian melanoma may be differentiated from the more common melanoma metastatic to the ovaries by its unilaterality, the presence of junctional change, and a detailed history and physical examination to exclude another primary site. Overall, 50% of patients with Stage I dermoid-associated melanoma were alive at 2 years compared with 89% of patients with Stage I dermoid-associated squamous carcinoma at 5 years. In the last 10 years, however, with the application o aggressive chemotherapy, survival has improved.

Female↗
PubMed1996

Fluid homeostasis after heart transplantation: the role of cardiac denervation.

BACKGROUND: Orthotopic heart transplantation may interrupt key neural and humoral homeostatic mechanisms that normally adjust Na+ and fluid excretion to changes in intake. Such an interruption could lead to plasma volume expansion. METHODS: We measured plasma volume and fluid regulatory hormones under standardized conditions in 11 heart transplant recipients (58 +/- 7 years old; mean +/- standard deviation) 21 +/- 4 months after transplantation, in 6 liver transplant recipients (51 +/- 6 years old) 13 +/- 8 months after transplantation (cyclosporine control group), and in 7 normal healthy control subjects (61 +/- 9 years old). Administration of all diuretics and antihypertensive drugs was discontinued before the study. After 3 days during which subjects ate a constant diet containing 87 mEq of Na+ per 24 hours, plasma volume was measured by a modified Evans blue dye (T-1824) dilution technique. Renal creatinine clearance was measured and blood samples were drawn for determination of plasma levels of vasopressin, angiotensin II, aldosterone, atrial natriuretic peptide, and plasma renin activity. RESULTS: Supine resting plasma renin activity, angiotensin II, and aldosterone (renin-angiotensin-aldosterone axis) and vasopressin levels were not different among the control, heart transplant, and liver transplant groups. However, there was a trend toward elevated angiotensin II (p < or = 0.08) and aldosterone (p < or = 0.08) levels in the heart transplant recipients. Atrial natriuretic peptide levels were significantly elevated two to threefold in the heart transplant recipients when compared with those in the two control groups. Blood volume, normalized for body weight (milliliters per kilogram), was significantly greater (14%) in the heart transplant recipients when compared with that in liver transplant recipients and normal healthy control subjects. Blood volume values did not differ (p > or = 0.05) between the two control groups. CONCLUSIONS: Extracellular fluid volume expansion (+14%) occurs in clinically stable heart transplant recipients who become hypertensive. Although hyperactivity of the renin-angiotensin-aldosterone axis is not apparent during supine resting conditions, our data suggest that the renin-angiotensin-aldosterone system is not responsive to a hypervolemic stimulus and this is likely a consequence of chronic cardiac deafferentation. Thus, poor adaptation of the renin-angiotensin-aldosterone system to fluid retention may be partly responsible for the incidence and severity of posttransplantation hypertension in some heart transplant recipients.

Aged↗
PubMed1995

Sensitivity of frozen section examination of pelvic lymph nodes for metastatic prostate carcinoma.

BACKGROUND: A Total Quality Improvement review of frozen section diagnoses yielded four sequential false-negative frozen section diagnoses in lymph nodes in the evaluation of metastases from prostate carcinoma. Because these results appeared to differ from the department's overall frozen section experience, frozen section diagnoses of pelvic lymph nodes in patients with prostate carcinoma were reviewed to benchmark the department's performance. METHODS: All 220 pelvic lymph node frozen section samples from 110 patients with prostate carcinoma from January, 1986 to July, 1993 at Bridgeport Hospital (BH) were reviewed, and the department's frozen section diagnostic efficiency was compared with: (1) all BH frozen section procedures performed during the same period; (2) pelvic lymph node frozen section analysis and (3) imaging techniques for prostate carcinoma from other institutions found in MEDLARS literature searches from 1973 to 1993. RESULTS: Frozen section diagnostic efficiency for patients with prostate carcinoma from BH was 93.6% (sensitivity 63.2%, specificity 100%) compared with (1) 98% for all BH frozen section analyses (sensitivity 99%, specificity 98%); (2) 90.1% for MEDLARS search pelvic lymph node frozen section prostate carcinoma analyses (sensitivity 66.5%, specificity 100%); and (3) 88% for MEDLARS search magnetic resonance imaging (MRI) pelvic lymph node prostate carcinoma (sensitivity 41%, specificity 97%). CONCLUSIONS: Frozen section diagnosis of pelvic lymph nodes approaches the overall diagnostic efficiency of frozen section analysis and is more sensitive for the diagnosis of prostate carcinoma in pelvic lymph nodes than is MRI because more than half of the metastases are smaller than the 1.0-cm resolution limit of the MRI. False-negative frozen section diagnoses (67% sensitivity) occur because of errors in sampling microscopic metastases.

Adenocarcinoma↗
PubMed1995

Significance of hepatic expression of hepatitis C viral antigens in chronic hepatitis C.

To determine the significance of hepatic expression of hepatitis C viral (HCV) antigens, HCV core and NS4 antigens were detected by immunohistochemistry in 46 patients with chronic HCV infection. Serum HCV RNA was quantitated by branched DNA assay in 41 and HCV genotype determined in 30 patients. HCV core and NS4 antigens were detected exclusively in the cytoplasm of hepatocytes in 83% and 61% of patients, respectively. There was no correlation between the expression of HCV antigens and clinical, biochemical, histological parameters and HCV genotype. Hepatic expression of HCV antigens was positively associated with serum HCV-RNA levels (P < 0.02). At the end of interferon-alpha (IFN) therapy, expression of HCV antigens remained either unchanged or decreased in 11/12 patients studied (undetectable in all four patients who had complete and sustained response). We conclude that hepatic expression of HCV core and NS4 antigens parallels serum HCV-RNA levels and IFN therapy reduces hepatic expression of these viral antigens.

Female↗
PubMed1995

alpha-Glutathione S-transferase as a marker of hepatocellular damage in chronic hepatitis C virus infection.

alpha-Glutathione S-transferase (alpha GST) may be a good serologic marker of hepatocellular damage because of its low molecular weight, uniform hepatic distribution, high cytosolic concentration, and short half-life. To determine the clinical utility of alpha GST in patients with chronic hepatitis C virus (HCV) infection, serum alpha GST levels were measured in 96 patients with chronic HCV infection, of whom 47 subsequently underwent interferon-alpha therapy. Patients were simultaneously evaluated with conventional liver biochemistry, serum HCV RNA levels, and liver histology. Different methods of serum collection did not affect alpha GST values, indicating that this was a stable serum marker. In 93% of patients with chronic HCV infection, alpha GST was elevated and showed an excellent correlation with serum aminotransferases. Histologic analysis revealed a correlation of alpha GST with both lobular inflammation and bile duct lesions. There was no correlation between serum alpha GST levels and the demographic features, mode of transmission, virologic, other histologic parameters, or subsequent response to interferon-alpha. During serial monitoring in patients undergoing interferon-alpha therapy, elevation of serum alpha GST correlated with biochemical relapse and in some patients virologic relapse in the presence of normal liver biochemistry. alpha GST was persistently elevated in all nonresponders. Four of six of those patients who responded completely followed by early relapse had elevated alpha GST intermittently or continuously during therapy despite normalization of serum aminotransferases. Two of five of those with a complete and sustained response had elevated alpha GST during treatment and follow-up, and both were also seropositive for HCV RNA during follow-up. These data demonstrate that alpha GST is a stable marker, has similar diagnostic utility as serum aminotransferases, and may have a role in the monitoring of patients undergoing interferon-alpha therapy.

Adult↗
PubMed1995

Application of six hepatitis C virus genotyping systems to sera from chronic hepatitis C patients in the United States.

Serum samples from 139 US patients with chronic hepatitis C virus (HCV) infection were studied using six different genotyping systems, including both molecular and serologic methods, to determine the applicability of these approaches and the prevalence of various HCV subtypes. The concordance of genotyping results based on the various systems (except for core polymerase chain reaction genotyping) was good (93.5%). Subtypes 1a and 1b were prevalent (37.4%). Subtypes 2a (2.2%), 2b (8.6%), and 3a (5.8%) were less common. HCV genotypes could not be determined in 3.4%-16.5% of samples depending on the method used. HCV type 2 was associated with greater histologic activity but lower serum HCV RNA levels (P < .05), whereas type 3 was associated with lower serum alanine aminotransferase levels (P < .05). These data demonstrate a high concordance between HCV genotyping systems and provide a foundation for comparison of genotyping data between studies using different systems. HCV types 1a and 1b are both prevalent in the United States.

Adult↗
PubMed1995

Plasma glutathione concentration in patients with chronic hepatitis C virus infection.

It has recently been proposed that a depletion of glutathione (GSH) may be a contributing factor to viral persistence and resistance to interferon-alpha (IFN-alpha) therapy in chronic hepatitis C virus (HC) infection. The aim of this study was: (1) to compare plasma GSH levels in patients with chronic HCV infection and normal healthy controls; and (2) to correlate GSH levels with liver histology and serum HCV RNA levels. Twenty-four patients with compensated chronic hepatitis C and 27 healthy subjects were studied. Serum and heparinized plasma were prospectively prepared and frozen within 1 h of collection. Plasma glutathione and glutathione peroxidase (GP) levels were measured spectrophotometrically. The serum HCV RNA level was quantitated by the branched chain DNA signal-amplification assay. Plasma GSH levels were not decreased in patients with chronic HCV infection but were actually greater than in controls (control 1.27 +/- 0.12 micrograms ml-1, HCV 1.62 +/- 0.11 micrograms ml-1, P < 0.05). There was also no difference in plasma GP activity between these two groups (control 0.233 +/- 0.007 U ml-1, HCV 0.230 +/- 0.007 U ml-1). Among the patients with chronic HCV infection, there was no correlation between either plasma GSH or GP levels and the serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST), serum HCV RNA level, or liver histology. This study demonstrates that chronic HCV infection does not decrease the plasma GSH and GP levels.

Adult↗
PubMed1995

Variations of hepatitis C virus NS5B sequence (nucleotides 8261-8566) do not correlate with response to interferon-alpha therapy.

Hepatitis C virus (HCV) is an RNA virus with the NS5B gene encoding an RNA-dependent RNA polymerase. Interferon-alpha (IFN-alpha) is effective against HCV and its effect is believed to be related to its antiviral activity. To determine whether sequence variations of the HCV NS5B region correlate with response to IFN therapy, pretreatment serum samples from 40 patients with chronic HCV infection who were subsequently treated with IFN (> or = 3 MU thrice weekly for 24 weeks) and had well-characterized biochemical responses were studied. Reverse transcription-polymerase chain reaction (RT-PCR) was performed to generate an approximately 365-bp fragment from which nucleotide sequence and genotypes were determined. By comparing the nucleotide sequences and the encoded amino acid sequences of samples from each group, no response group-specific nucleotide or encoded amino acid substitution was identified. Most of the substitutions identified were synonymous (usually by changes at the third position of the codon). These data suggest that these substitutions were selective rather than spontaneous events. Of the few non-synonymous substitutions identified, none was correlated with subsequent response to IFN, either within or across genotypes.

Adult↗
PubMed1995

Choice of appropriate end points of response to interferon therapy in chronic hepatitis C virus infection.

Current definitions of response to interferon (IFN) depend upon decreasing the serum alanine aminotransferase (ALT) level to normal during therapy. Although this complete response is often associated with loss of detectable hepatitis C virus (HCV) in serum, the frequent occurrence of relapse indicates that eradication of the virus is not achieved. Thus, consideration of more meaningful end points for IFN response is necessary. To begin to define a more effective end point, we recently tested serial serum samples from 15 patients with three different biochemical response patterns (five patients, no response; five, complete response with relapse; five, complete and sustained response) for HCV-RNA by both reverse transcription polymerase chain reaction (RT-PCR) and branched DNA signal amplification assay. In the IFN nonrespondes, HCV-RNA was detected in serum and liver at completion of IFN therapy in all five patients. Similarly, in the complete responders followed by relapse, HCV-RNA was still detected in serum and liver at the end of IFN therapy in four and five patients, respectively, despite complete normalization of serum ALT. In the complete and sustained responders, HCV-RNA was detected in serum and liver at completion of IFN therapy in only one and no patients, respectively. However, all five sustained biochemical responders had virologic relapse detected at one or more time points within 6 months after cessation of IFN therapy despite persistently normal ALT. HCV-RNA remained detectable in serum at the pretreatment level without biochemical abnormalities for a range of 1 1/4 to 3 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic Disease↗
PubMed1994

Transplantation of a hepatitis B surface antigen-positive donor liver into a hepatitis B virus-negative recipient.

A critically ill, HBV seronegative girl who received a liver from a HBsAg+ donor is described. Despite HBV Ig prophylaxis, she was seropositive for HBsAg shortly after transplantation. Although the postoperative period was complicated, HBV-related problems were not encountered. Liver dysfunction was noted 7 months after transplantation. At that time, she became anti-HBc IgM-positive, with liver histologic findings suggestive of chronic active hepatitis B. The liver function normalized after a reduction of immunosuppressive therapy and introduction of ciprofloxacin. The patient had low level HBV replication during the entire follow-up period (HBV DNA-positive by PCR only) and sequencing of the virus on 4 occasions revealed only wild-type HBV. She subsequently lost serum HBsAg and HBV DNA (even by PCR) and has remained well 2 years after transplantation.

Base Sequence↗
PubMed1994

Hepatocyte proliferation as an indicator of outcome in acute alcoholic hepatitis.

To determine whether clinical outcome in patients with acute alcoholic hepatitis is related to the regenerative capability of the liver, liver biopsy specimens from 25 prospectively recruited patients with acute alcoholic hepatitis were studied for hepatic expression of mRNA for two proliferation markers, proliferating cell nuclear antigen and human histone, and for transforming growth factor alpha (TGF alpha) and TGF beta 1 and hepatocyte growth factor (HGF), which regulate hepatocyte proliferation. Proliferation markers were detected to varying degrees in 0-80% of hepatocytes and occasionally in sinusoidal cells and bile-duct epithelium in 19 patients (76%). Patients who survived for 6 months had greater expression of proliferation markers than those who did not survive (p < 0.01). TGF alpha was detected in hepatocytes and bile-duct epithelium, whereas TGF beta 1 was detected mainly in sinusoidal cells and was associated with perivenular fibrosis. Patients who survived for 6 months had greater expression of TGFs than non-survivors (p < 0.02). HGF was detected in sinusoidal cells in 7 patients and correlated with survival (p < 0.01). These data indicate that hepatocyte proliferation, which is possibly related to the pattern of hepatotrophic factor expression, is a good indicator of outcome in acute alcoholic hepatitis.

Acute Disease↗
PubMed1994

Interferon treatment of chronic hepatitis C.

The natural history of chronic hepatitis C is just beginning to be clarified, with its more common course being an insidiously progressive liver disease that often remains clinically inconsequential for many years or even decades. Although chronic hepatitis C progresses histologically, the impact on the clinical well-being of the patient is less evident. Interferon is an effective therapy for this disease because of its antiviral effect on the cytopathic hepatitis C virus, lowering serum alanine aminotransferase (ALT) levels, rather than because of any immune modulatory mechanism. Unfortunately, interferon therapy does not permanently eradicate hepatitis C virus in the majority of patients, and relapse with return of the serum ALT level to the pretreatment range occurs in approximately 70% of responding patients. Other interferon-treated patients continue to be viremic and are not considered to be responders. In addition, not all patients with chronic hepatitis C require treatment. A systematic approach to patient evaluation is necessary to determine the need for treatment, assess treatment response, identify side effects of therapy, and assist in other clinical decisions.

Chronic Disease↗
PubMed1994

Acute Streptococcus pneumoniae meningogenic labyrinthitis. An experimental guinea pig model and literature review.

OBJECTIVE: To create an experimental model of Streptococcus pneumoniae type 3 meningogenic labyrinthitis (a leading cause of deafness) similar to that in human disease. DESIGN: Cohort analytic study of guinea pigs that were inoculated intrathecally with varying dilutions of S pneumoniae type 3; the progress of the disease was compared with that in saline solution-inoculated control animals. SUBJECTS: Healthy adult Hartley guinea pigs without clinical evidence of middle ear disease that were conveniently sampled. INTERVENTIONS: Intrathecal inoculation of 10(4) to 10(6) colony-forming units of S pneumoniae type 3 into 13 guinea pigs; signs and symptoms of meningitis/labyrinthitis were observed for 15 days and compared with those in two saline solution-inoculated control animals. MAIN OUTCOME MEASURES: Morbidity--labyrinthitis, meningitis; end point--death. RESULTS: The 10(4) to 10(6) colony-forming units of S pneumoniae type 3 caused inflammation that extended from the meninges to the inner ear via the cochlear aqueduct within 3 days after inoculation; a dose of 10(7) killed animals within 12 hours after inoculation. Three of five animals that were inoculated with a 10(6) dose died 3 days after inoculation; two of three animals that were inoculated with a 10(5) dose lived to 15 days after inoculation. One of two animals that were inoculated with a 10(4) dose did not become infected. Inflammation extended to the middle ear by round-window destruction. Reactive bone formation simulated labyrinthine osteosclerosis. Observers assessed histologic slides "blindly." CONCLUSION: Guinea pigs can survive 15 days after intrathecal inoculation of a 10(5) dose, with morphologic features similar to those in human disease. This is an effective model for this study of meningogenic labyrinthitis.

Acute Disease↗
PubMed1994

Detection of hepatitis C virus RNA genome in liver tissue by nonisotopic in situ hybridization.

A rapid technique for the detection of hepatitis C virus (HCV) RNA in liver section using nonisotopic in situ hybridization was described. Only 3 of the 10 patients seropositive for antibody to HCV and HCV RNA had detectable HCV RNA in the hepatocytes (1%, 2%, and 15% of cells positive). No specific signal was detected in sinusoidal, biliary epithelial, and mononuclear cells. The positive hepatocytes were scattered in the liver lobule with occasional clusters. The positive signal was confined to the cytoplasmic compartment. These data support the previous observation of the hepatocyte tropism of HCV.

Adult↗