Search PubMed⌕ Search

Biomedical subjects

D Neal

Publications and source records attributed to D Neal.

At least 37 records · Page 2Linked to original sources
PubMed1995

Evidence that the brain of the conscious dog is insulin sensitive.

The aim of this study was to determine whether a selective increase in the level of insulin in the blood perfusing the brain is a determinant of the counterregulatory response to hypoglycemia. Experiments were carried out on 15 conscious 18-h-fasted dogs. Insulin was infused (2 mU/kg per min) in separate, randomized studies into a peripheral vein (n = 7) or both carotid and vertebral arteries (n = 8). This resulted in equivalent systemic insulinemia (84 +/- 6 vs. 86 +/- 6 microU/ml) but differing insulin levels in the head (84 +/- 6 vs. 195 +/- 5 microU/ml, respectively). Glucose was infused during peripheral insulin infusion to maintain the glucose level (56 +/- 2 mg/dl) at a value similar to that seen during head insulin infusion (58 +/- 2 mg/dl). Despite equivalent peripheral insulin levels and similar hypoglycemia; steady state plasma epinephrine (792 +/- 198 vs. 2394 +/- 312 pg/ml), norepinephrine (404 +/- 33 vs. 778 +/- 93 pg/ml), cortisol (6.8 +/- 1.8 vs. 9.8 +/- 1.6 micrograms/dl) and pancreatic polypeptide (722 +/- 273 vs. 1061 +/- 255 pg/ml) levels were all increased to a greater extent during head insulin infusion (P < 0.05). Hepatic glucose production, measured with [3-3H]glucose, rose from 2.6 +/- 0.2 to 4.3 +/- 0.4 mg/kg per min (P < 0.01) in response to head insulin infusion but remained unchanged (2.6 +/- 0.5 mg/kg per min) during peripheral insulin infusion. Similarly, gluconeogenesis, lipolysis, and ketogenesis were increased twofold (P < 0.001) during head compared with peripheral insulin infusion. Cardiovascular parameters were also significantly higher (P < 0.05) during head compared with peripheral insulin infusion. We conclude that during hypoglycemia in the conscious dog (a) the brain is directly responsive to physiologic elevations of insulin and (b) the response includes a profound stimulation of the autonomic nervous system with accompanying metabolic and cardiovascular changes.

3-Hydroxybutyric Acid↗
PubMed1995

Resection of giant invasive pituitary tumors through a transfacial approach: technical case report.

Giant invasive pituitary adenomas are rare tumors that have been reported to extensively involve the cranial base, as well as other intra- and extra-cranial structures, making surgical resection by traditional approaches impossible. We report two cases, each of a giant invasive adenoma involving the entire length of the clivus and adjacent structures that was resected via a transfacial approach with excellent results. Both tumors were in middle-aged men; one was nonsecreting, and the other secreted follicle-stimulating hormone alpha-subunit. Most previously reported giant invasive adenomas have been prolactinomas. Both tumors were resected via a transfacial approach that incorporated an osteoplastic maxillotomy with palatal division and a posterior pharyngeal incision that provided exposure from the suprasellar region to C2. Both of the patients received postoperative radiation and have done very well. Their cosmetic results were excellent. The complications included postoperative meningitis in one patient and a nasal voice in the other. The transfacial approach provides excellent access for this type of extensive midline tumor requiring resection from the suprasellar region down to the foramen magnum.

Adenoma↗
PubMed1994

Warfarin treatment and migraine.

A patient suffering from migraine, whose symptoms were abolished by warfarin therapy, is reported. Warfarin was prescribed for deep vein thrombosis and the frequency of the patient's headache improved remarkably during the anticoagulant therapy. Because of the unusual nature of the response to anticoagulant therapy, warfarin was reintroduced on a double blind (versus placebo) basis and once again abolished the headaches.

Aged↗
PubMed1994

Disposition of a mixed meal by the conscious dog.

The disposition of a mixed meal administered intragastrically was examined in 13 24-h-fasted conscious dogs, using the arteriovenous (AV) difference technique (and isotopic methods in 6 dogs). Postprandial net gut output totaled (in g of glucose equivalents) 42 +/- 6 glucose, 3 +/- 0.3 lactate, 2 +/- 0.2 alanine, and 0.2 +/- 0.0 glycerol. The gut oxidized 2 +/- 1 g of glucose, and 0.2 +/- 0.1 g remained within the intestinal lumen. Of the administered glucose 68 +/- 6% were accounted for, and volatile fatty acid production by the gut (n = 1) accounted for at least an additional 4%. Of the labeled glucose in the meal 82 +/- 5% appeared in the systemic circulation, an apparent overestimate of absorption of glucose from the meal. Cumulative net hepatic uptakes (in g of glucose equivalents) were 4.1 +/- 3.1 glucose, 12.1 +/- 2.1 gluconeogenic amino acids, and 1.5 +/- 0.2 glycerol. Net hepatic glycogen synthesis and lactate and CO2 production accounted for 6.2 +/- 4.1, 9.3 +/- 2.8, and 1.6 +/- 0.8 g of glucose equivalents, respectively. In summary, the AV difference method could account for the gut disposition of about two-thirds of the meal glucose. Nonsplanchnic tissues disposed of threefold more glucose than the liver. Net hepatic uptake of glucose equivalents as gluconeogenic amino acids was threefold > glucose uptake, and net hepatic uptake of gluconeogenic amino acids was > net gut release of gluconeogenic amino acids. In conclusion, the net hepatic uptake of glucose and gluconeogenic substrates provided adequate carbon for net hepatic synthesis of glycogen and production of lactate and CO2. In a net sense, peripheral tissues must have been the source of some of the gluconeogenic carbon taken up by the liver after the meal.

Amino Acids↗
PubMed1994

Contraindications and complications of laparoscopic cholecystectomy.

Laparoscopic cholecystectomy is a commonly performed procedure for the removal of symptomatic gallstones. Compared with open cholecystectomy, laparoscopic cholecystectomy is associated with less postoperative pain, earlier discharge from the hospital and a more rapid recovery. However, there are specific contraindications to the procedure, including empyema of the gallbladder, gangrenous cholecystitis, coagulopathy, portal hypertension and peritonitis. Complications from laparoscopic cholecystectomy include common duct injury, bleeding, bile leakage and wound infection. An understanding of these issues allows the family physician to more appropriately select patients for laparoscopic removal of the gallbladder.

Cholecystectomy, Laparoscopic↗
PubMed1993

Levels of matrix metalloproteases in bladder cancer correlate with tumor grade and invasion.

We have used quantitative zymography to measure levels of the type IV collagenases matrix metalloproteinase (MMP)-9 and MMP-2 in 42 biopsies of transitional cell carcinoma and in 7 biopsies of normal bladder. Mean levels of MMP-9 were significantly higher in tumor compared with normal samples (P = 0.08). Levels of MMP-9 and active MMP-2 increased with tumor grade (test for trend, P = 0.002 and P = 0.05, respectively). Levels of MMP-9 and activated MMP-2 were also higher in invasive tumors than in superficial ones (P = 0.001 and P = 0.008, respectively). In situ hybridization studies showed that the mRNAs for both MMP-2 and MMP-9 were located chiefly in the stroma rather than epithelial tumor cells and were concentrated at the interface between the two tissues.

Carcinoma, Transitional Cell↗
PubMed1993

Clinical utilization and complications of sural nerve biopsy.

Surgeons frequently perform sural nerve biopsy as part of the work-up of patients with peripheral neuropathy. The indications for the procedure, therapeutic value, and complications associated with the procedure have received little attention in the surgical literature. A retrospective chart review of 60 patients with the suspected diagnosis of peripheral neuropathy undergoing sural nerve biopsy was performed. Vasculitis was suspected in 29 (48%) patients undergoing biopsy. This diagnosis was confirmed in 6 of the 29 patients and resulted in the alteration of therapy in 31% of patients with this suspected diagnosis. In 27 (45%) patients, the etiology of their peripheral neuropathy was unknown. Twelve (44%) patients in this group had sural nerve pathology; however, no change in therapy was required. Ten patients in our series had associated malignant tumors; some of these patients were diagnosed after referral for sural nerve biopsy. Twenty-five (42%) patients remained undiagnosed after biopsy. Nerve conduction studies were performed in 14 (22%) patients. Thirteen patients with abnormal lower extremity nerve conduction studies had 6 normal and 7 abnormal biopsy results. The one patient with a normal study had a normal nerve biopsy result. There were six (10%) patients with wound infections, seven (12%) patients with delayed wound healing, and three (5%) patients with new onset of chronic pain in the distribution of the sural nerve, for an overall complication rate of 27%. There was no correlation between the preoperative use of antibiotics, type of local anesthetic used, or length of nerve excised and complication rate. We conclude that the complication rate after sural nerve biopsy is significant. Strict criteria should be employed in selecting patients for sural nerve biopsy including a careful neurologic history and physical examination, nerve conduction studies, appropriate work-up for vasculitis if suspected, and implementation of a search for malignancy if this is not apparent. If the diagnosis is still in question, then sural nerve biopsy would seem appropriate, especially in patients with suspected vasculitis.

Adult↗
PubMed1993

Effects of hyperinsulinemia on the subsequent hormonal response to hypoglycemia in conscious dogs.

The aim of this study was to determine if differing periods of prior hyperinsulinemic nonhypoglycemia can modify the subsequent counterregulatory response to hypoglycemia. Experiments were carried out on 19 normal 18-h fasted conscious dogs. Insulin was infused intraportally at 8 mU.kg-1.min-1 for 3 h on two occasions and 3.5 h on a third separate occasion. This resulted in similar steady-state arterial insulin levels during each protocol (4,370 +/- 433 pmol/l). Each animal was maintained at a similar plasma glucose nadir (2.8 +/- 0.6 mmol/l) for 2 or 2.5h, depending on the protocol. In protocol I (n = 7) plasma glucose was allowed to fall to the desired hypoglycemic plateau by 30 min. In a second group of dogs (protocol II, n = 5) there was a 30-min period of euglycemic hyperinsulinemia followed by a 30-min fall (similar to protocol I) in plasma glucose. In a third group of dogs (protocol III, n = 7), there was an initial 15-min period of euglycemic hyperinsulinemia followed by a 45-min fall in plasma glucose. Differing periods of euglycemic hyperinsulinemia had distinct effects on subsequent counterregulation. During the final 2 h of hypoglycemia the incremental area under the curve (AUC) for glucagon was significantly greater in protocol I vs. II (3.0 +/- 1.0, -0.5 +/- 0.2 micrograms.l-1.min-1, P < 0.02, respectively). Conversely, catecholamine levels were increased in protocol II (30 min prior hyperinsulinemic euglycemia) compared with protocol I (epinephrine 1,448 +/- 268, 855 +/- 119 nmol.l-1.min-1; norepinephrine 244 +/- 30, 166 +/- 23 nmol.l-1.min-1, respectively, P < 0.05). During protocol III, glucagon and catecholamine levels were intermediate between protocols I (no euglycemic hyperinsulinemia) and II (30 min euglycemic hyperinsulinemia).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Impact of chronic stress hormone infusion on hepatic carbohydrate metabolism in the conscious dog.

The effects of chronic administration of counterregulatory hormones on hepatic glycogenolysis and gluconeogenesis were investigated. We studied 14 20-h fasted conscious dogs prior to (day 0) and after a 70-h stress hormone (SHI, n = 7) or saline (n = 7) infusion (day 3). Glucose production and gluconeogenesis were assessed using tracer and arteriovenous difference techniques. SHI increased plasma glucagon, cortisol, epinephrine, and norepinephrine levels approximately fivefold. SHI increased the arterial plasma glucose and insulin concentrations (110 +/- 2 to 204 +/- 19 mg/dl and 13 +/- 2 to 36 +/- 3 microU/ml on day 3). Tracer-determined glucose appearance and net hepatic glucose output were increased 80 and 60%, respectively. Net hepatic lactate uptake and fractional extraction were increased by 11.2 +/- 3.8 and 0.51 +/- 0.18 mumol.kg-1 x min-1, respectively, as was net hepatic glycerol uptake (1.0 +/- 0.6 mumol.kg-1 x min-1). Net hepatic fractional alanine extraction was also increased by 0.37 +/- 0.03 mumol.kg-1 x min-1; however, net hepatic alanine uptake was not altered. The efficiency of alanine conversion to glucose almost doubled (0.33 +/- 0.05 to 0.59 +/- 0.09). Renal glucose production was also increased, accounting for 33% of the increase in glucose turnover. This increase was paralleled by an increase in renal gluconeogenic precursor uptake. In conclusion, SHI created marked hyperglycemia and hyperinsulinemia and elevated glucose production from both the liver and the kidney, with gluconeogenesis accounting for approximately 70% of the response.

Animals↗
PubMed1993

Effect of hepatic nerves on disposition of an intraduodenal glucose load.

We examined the disposition of a continuous 4-h intraduodenal glucose infusion (8 mg.kg-1 x min-1, labeled with [1-13C]glucose and [3-3H]glucose) in nine conscious hepatic-denervated dogs. Cumulative net hepatic uptakes (in grams of glucose equivalents) were 13.7 +/- 2.5 glucose, 3.1 +/- 0.6 gluconeogenic amino acids, and 0.8 +/- 0.1 glycerol. Net hepatic glycogen synthesis totalled 11.0 +/- 0.9 g, 55-62% via the direct pathway. All values were similar to those in hepatic-innervated dogs. Glycogen synthase activity and rate of glycogen synthesis were positively correlated (r2 = 0.913, P < 0.05). Variability in net hepatic glycogen synthesis and the mass of glycogen synthesized via the indirect pathway was reduced in hepatic-denervated dogs (P < 0.05). In conclusion, the glycemic response and rate of net glycogen synthesis during an intraduodenal glucose infusion was no different in hepatic-denervated and -innervated dogs. Net hepatic glucose uptake was sufficient to account for all net hepatic glycogen synthesis and lactate production, consistent with an intrahepatic source of gluconeogenic precursors for glycogen synthesis via the indirect pathway. Hepatic nerves appear responsible for much of the variability in net hepatic glycogen synthesis and in the mass of glycogen synthesized via the indirect pathway in normal dogs.

Amino Acids↗
PubMed1992

Effects of differing insulin levels on response to equivalent hypoglycemia in conscious dogs.

The aim of this study was to determine if differing concentrations of insulin can modify the counterregulatory response to equivalent hypoglycemia. Insulin was infused intraportally into normal 18-h-fasted conscious dogs at 2 (low, n = 6) or 8 mU.kg-1.min-1 (high, n = 7) on separate occasions. This resulted in steady-state arterial insulin levels of 80 +/- 8 and 610 +/- 55 microU/ml, respectively. Glucose was infused during the high dose to maintain plasma glucose similar to low (50 +/- 1 mg/dl). Despite similar plasma glucose levels, epinephrine (2,589 +/- 260, 806 +/- 180 pg/ml), norepinephrine (535 +/- 60, 303 +/- 55 pg/ml), cortisol (12.1 +/- 1.5, 5.8 +/- 1.2 micrograms/dl), and pancreatic polypeptide (1,198 +/- 150, 598 +/- 250 pg/ml) were all increased in the presence of high-dose insulin (P < 0.05). Glucagon levels were similar during both insulin infusions. Hepatic glucose production, measured with [3-3H]-glucose, rose from 2.6 +/- 0.2 to 4.7 +/- 0.3 mg.kg-1.min-1 in response to high insulin (P < 0.01) but remained unchanged, 3.0 +/- 0.5 mg.kg-1.min-1, during low-dose infusions. Six hyperinsulinemic euglycemic control experiments (2 or 8 mU.kg-1.min-1, n = 3 in each) provided baseline data. By the final hour of the high-dose euglycemic clamps, cortisol (2.4 +/- 0.4 to 4.8 +/- 0.8 micrograms/dl) and norepinephrine (125 +/- 34 to 278 +/- 60 pg/ml) had increased (P < 0.05) compared with baseline. Plasma epinephrine levels remained unchanged during both series of euglycemic studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Cytogenetic profile of 109 lipomas.

Cytogenetic analysis of short-term cultures was carried out on 109 lipomas from 92 patients. Clonal chromosomal abnormalities were present in 50% of the tumors analyzed. Based on the results, three main cytogenetic groups were identified and included: (a) tumors with normal karyotypes, (b) tumors with abnormalities involving region q13-15 on chromosome 12, and (c) tumors with other clonal aberrations. Within each of these groups, cytogenetic subgroups could be identified, each characterized by a specific anomaly. Tumors with abnormalities of 12q included specific subgroups with t/ins(1;12)(p32-33;q13-15), t(2;12)(p21-22;q13-14), t(3;12)(q28;q14), t(12;21)(q13;q21), complex, and nonrecurrent aberrations. The group containing heterogeneous clonal aberrations included subgroups with del(13)(q12q22), der(6)(p21-23), der(11)(q13), and nonspecific aberrations. Chromosome bands 1p36, 1p32-33, 2p21-22, 3q27-28, 6p21-23, 11q13, 12q13-15, 13q12, 13q22, 17p13, 17q21, and 21q21-22 were preferentially involved in structural rearrangements in lipomas. The identification of these sites of nonrandom rearrangements may serve to identify genes (at or near the junctions of chromosomal aberrations) involved in normal cellular growth control. Statistical analysis of the data revealed a correlation among karyotypic abnormalities and clinical data, such as age and sex of the patient, and tumor depth, site, and size.

Chromosome Aberrations↗
PubMed1991

Progressive multifocal leukoencephalopathy in persons infected with human immunodeficiency virus, San Francisco, 1981-1989.

Progressive multifocal leukoencephalopathy (PML), a rare neurological disease, has been sporadically reported in persons infected with human immunodeficiency virus (HIV), the causative agent of acquired immune deficiency syndrome (AIDS). From January 1981 through February 1989, in San Francisco, we identified 94 HIV-infected persons with PML, of whom 48 (51%) were pathologically confirmed (as required for AIDS case reporting). These 48 patients were significantly older when diagnosed with AIDS (20% older than 50 years) than patients with AIDS without PML. The remaining 46 (49%) patients, diagnosed clinically and by neuroimaging, did not differ significantly from definitive patients in demographic or survival characteristics after PML diagnosis. We detected antibodies to JC virus, the causative agent of PML, in 9 of 14 (64%) AIDS-related patients with PML, and in 9 of 14 (64%) matched control subjects, suggesting that determination of JC virus antibody status before AIDS diagnosis does not reliably indicate which patients will contract PML. Our study shows that the proportion of patients with AIDS who contracted PML remained stable between 1981 and 1988, but increased in the first 2 months of 1989. Our findings further indicate that PML in HIV-infected patients may be underestimated by as much as 50%.

Adolescent↗
PubMed1990

The partial purification and characterization of GnRH-like activity from prostatic biopsy specimens and prostatic cancer cell lines.

We have investigated the possibility of the secretion of gonadotrophin-releasing-hormone (GnRH)-like peptides by prostatic cancer cells in culture and their presence in cytosolic preparations from human prostatic biopsy specimens. A GnRH-specific radioimmunoassay showed GnRH-like activity in concentrated cytosolic preparations and conditioned media from DU 145, an androgen-insensitive human prostatic cell line and from LNCaP, an androgen-responsive prostatic cancer cell line. GnRH immunoreactivity in culture media correlated directly with cell numbers. HPLC demonstrated that this GnRH-like material co-migrated with synthetic GnRH. This homology between synthetic GnRH and partially purified prostatic GnRH was confirmed following V8 protease and trypsin digestion which resulted in similar alterations in HPLC characteristics. The mean content of GnRH-like activity/g specimen tissue was significantly more in malignant tissue (88.5 +/- 80.5 fmol) than in benign (29.6 +/- 22 fmol), though more specimens of benign tissue were positive (37/54) than malignant tissue (6/22). This observation, taken with an earlier finding of GnRH-specific receptors in a hormone-sensitive cell line and human cancer specimens provides supportive evidence for the autocrine hypothesis of cell regulation.

Gonadotropin-Releasing Hormone↗
PubMed1990

Survival trends for patients with AIDS.

To evaluate trends in the length of survival for patients with acquired immunodeficiency syndrome, we calculated survival following diagnosis of acquired immunodeficiency syndrome for 4323 cases reported in San Francisco, Calif, between July 1981 and December 31, 1987. Patients were followed up prospectively through December 31, 1988. The median survival for all patients was 12.5 months, with a 5-year survival rate of 3.4%. Significantly improved survival was observed for patients diagnosed with Pneumocystis carinii pneumonia in 1986 and 1987. Survival for patients diagnosed with Kaposi's sarcoma declined significantly between 1981 and 1987. Survival was unchanged among patients diagnosed with other opportunistic infections or malignancies. Proportional hazards analyses indicated that initial diagnosis, age, and year of diagnosis were significant predictors of survival. For a subset of patients (n = 644), therapy with zidovudine was an additional significant predictor of survival. This study suggests that survival following diagnosis of acquired immunodeficiency syndrome has improved in recent years, primarily among patients with carinii pneumonia. Therapy with zidovudine may be partially responsible for these recent improvements.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Chronic hyperinsulinemia decreases insulin action but not insulin sensitivity.

Hyperinsulinemia and insulin resistance are commonly seen in obese and non-insulin-dependent diabetes mellitus (NIDDM) patients, suggesting a causal link exists between hyperinsulinemia and insulin resistance. In a previous study, we demonstrated that chronic (28 days) intraportal hyperinsulinemia (50% increase in basal insulin levels) resulted in a decrease in insulin action as assessed by a one-step euglycemic hyperinsulinemic clamp. Since only one dose of insulin was used during the clamp, it was not possible to determine if the decrease in insulin action was due to a change in insulin sensitivity and/or maximal insulin responsiveness. In the present study, insulin resistance was induced as before, but insulin action was assessed in overnight fasted conscious dogs using a four-step euglycemic hyperinsulinemic clamp (1, 2, 10, and 15 mU/kg/min). Insulin responsiveness was assessed before the induction of chronic hyperinsulinemia (day 0), and after 28 days of hyperinsulinemia (day 28). Transhepatic glucose balance and whole-body glucose utilization were measured to allow assessment of both the hepatic and peripheral effects of insulin. Chronic hyperinsulinemia increased basal insulin levels from 13 +/- 2 to 21 +/- 4 microU/mL. After 4 weeks of chronic hyperinsulinemia, maximal insulin-stimulated glucose utilization was decreased 23% +/- 4% (P less than .05) and insulin sensitivity (ED50) was not significantly altered. During the four-step clamp, the liver was a major site of glucose utilization. The liver was responsible for 13% of the total glucose disposal rate on day 0 (2.9 mg/kg/min) at the highest insulin infusion rate (15 mU/kg/min; 2,000 microU/mL).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Clearance from dialysate and equilibration of intraperitoneal vancomycin in continuous ambulatory peritoneal dialysis.

This article reports on a study of the disposition of loading doses (1g and 15 mg/kg) of vancomycin given intraperitoneally to 6 patients on continuous ambulatory peritoneal dialysis with Gram-positive peritonitis. Dialysate samples were collected every 30 minutes during the first dwell, and serum samples were collected after the first 5 exchanges and after 7 or 14 days. The dialysate concentration/time data were fitted to a monoexponential curve for 4 patients and to a biexponential curve for 2 others. Dialysis clearance was 0.73 +/- 0.04 L/h (1g dose) and 0.70 +/- 0.23 L/h (15 mg/kg dose). Total body clearance was 0.51 +/- 0.36 L/h. Serum concentrations reached 14 to 18 mg/L (15 mg/kg dose) and 6.75 to 24 mg/L (1g dose) at the end of the first dwell. The half-life of equilibration of vancomycin across the peritoneal membrane was 2.5 +/- 2.3 hours. Intraperitoneal loading doses of vancomycin produce concomitant serum concentrations in excess of the minimum inhibitory concentrations for susceptible organisms. Administration on a milligram per kilogram basis produces more consistent serum concentrations than using a standard loading dose which is not based on bodyweight.

Adolescent↗