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Biomedical subjects

D Sherlock

Publications and source records attributed to D Sherlock.

14 recordsLinked to original sources
PubMed1994

Cytochemical characteristics of neurons in the trigeminal mesencephalic nucleus of hatchling chicks.

The goal of the present study was to identify cytochemical markers characteristic of muscle afferents in hatchling chicks. To this end, we stained neurons in the trigeminal mesencephalic nucleus with a variety of markers that label subsets of neurons in avian dorsal root ganglia. We found that trigeminal mesencephalic neurons are surprisingly heterogeneous in their cytochemical make-up, expressing, to varying degrees, substance P, cholecystokinin, carbonic anhydrase, calbindin D-28k, parvalbumin, and S-100 beta. Calbindin D28k and S-100 beta appeared to be expressed equally in medial and lateral divisions of the trigeminal mesencephalic nucleus. In contrast, substance P- and cholecystokinin-immunoreactive neurons were more abundant in the medial division, whereas carbonic anhydrase activity and parvalbumin immunoreactivity were stronger in the lateral division. We were unable to detect met-enkephalin, neuropeptide Y, calcitonin gene-related peptide, vasoactive intestinal peptide, somatostatin, gamma-aminobutyric acid, or tyrosine hydroxylase in the trigeminal mesencephalic nucleus. Moreover, these neurons did not appear to bind the lectin Dolichos biflorus agglutinin. The heterogeneity of expression of markers among trigeminal mesencephalic nucleus neurons, especially between neurons in the medial and lateral divisions, suggests that these neurons are functionally diverse.

Animals↗
PubMed1992

Primary treatment of hepatocellular carcinoma by arterial chemoembolization.

Two hundred and ninety-one patients with hepatocellular carcinoma were treated by chemoembolization (CE), using ethiodized oil, doxorubicin, and a gelatin sponge. Patients with thrombosis of either the portal vein or a main branch were excluded. The mortality rate in the first 2 months after treatment was 7% in noncirrhotic patients, 2.8% in patients with class A cirrhosis, 8% in patients with class B cirrhosis, and 37% in patients with class C cirrhosis. The tumor diameter remained the same in 55.3% of patients, was reduced by up to 50% in 20% of the patients, was reduced by more than 50% in 7.3% of the patients, and almost completely disappeared in 1.8% of the patients. The diameter of the tumor increased in 15.6% of patients. Forty-three patients underwent a resection or transplantation after chemoembolization. Histologic examination of the specimens revealed significant necrosis of the tumor. The long-term survival rate at 2 years was 49% for class A cirrhotics, 29% for class B cirrhotics, and 9% for class C cirrhotics. Complications included cholecystitis (10%), vasculitis (14%), renal decompensation (13%), an increase in ascites (14%), and jaundice (12%). Chemoembolization is an effective and safe initial treatment for hepatocellular carcinoma. It is effective in producing tumor necrosis and reducing the size of the tumor. Improvement in survival was noted when patients who underwent chemoembolization were compared with an historical series of untreated patients, and resection and transplantation are kept as options.

Adolescent↗
PubMed1990

Options for elective treatment of portal hypertension in cirrhotic patients in the transplantation era.

We review herein our experience in the management of bleeding esophageal varices in cirrhotic patients and consider our findings in light of the dramatic changes in the treatment of cirrhosis resulting from the more widespread use of orthotopic liver transplantation (OLT). It does not seem realistic, at present, to propose OLT as the only effective treatment of variceal bleeding for a variety of reasons, and there remains a large group of patients who are noncompliant or unsuitable for liver transplantation. We propose that initial bleeding be controlled by endoscopic sclerotherapy, thereby allowing careful evaluation to be made electively. Grade A patients appear to be managed best by a reduced-size portacaval shunt (RPS) with prospects of good survival and few complications. Grade B patients can be managed by either sclerotherapy, RPS, or OLT, depending upon individual circumstances. Grade C patients are best managed by liver transplantation, again with excellent survival. In those grade C patients not deemed suitable for OLT (especially alcoholic patients), long-term endoscopic sclerotherapy is the best option. Changes in patient status may sometimes require revision of the treatment decision.

Adolescent↗
PubMed1989

The role of serotonin in the canine secretory response to cholera toxin in vivo.

This study was initiated to evaluate the role of serotonin in cholera toxin-induced jejunal secretion of water and electrolytes. Chronic Thiry-Vella loops, constructed in six dogs, were perfused with an isosmotic neutral perfusate containing [14C]polyethylene glycol as the recovery marker. Fluxes of water, sodium, chloride and potassium were calculated and immunoreactive serotonin levels were measured in blood and effluent perfusates. Intraluminal application of 20 micrograms of cholera toxin induced secretion; fluxes of water (basal, 32.3 +/- 11.1; 6 hr, -541 +/- 35 microliter/min), sodium (basal, 9.0 +/- 2.8; 6 hr, -78.3 +/- 5.6 microEq/min), chloride (basal, 3.8 +/- 1.5; 6 hr, -65.7 +/- 4.0 muEq/min) and potassium (basal, 0.10 +/- 0.08; 6 hr, -2.80 +/- 0.18 muEq/min) were all significantly different from basal. Serum electrolytes remained normal, except that potassium fell from 4.9 +/- 0.5 to 3.9 +/- 0.2 mEq/l. Although circulating serotonin levels did not change from base line (180.9 +/- 29.3 ng/ml), effluent concentrations increased significantly from 68.2 +/- 4.6 to 81.1 +/- 5.0 ng/ml (at 3 hr) and jejunal outputs increased from 136.6 +/- 10.2 to 205.1 +/- 10.1 ng/min (at 6 hr). In a separate set of experiments, verapamil was infused i.v. (12.5 micrograms/kg/min) during the 4th hr in four dogs exposed to cholera toxin. The lower dose of toxin (5 micrograms) induced secretion which was unaffected by the calcium channel blocker. In another series of studies, ketanserin (a 5-HT2 receptor blocker) was infused i.v. at 33 micrograms/kg/min during the 4th hr in four additional dogs exposed to the lower dose of cholera toxin. This potent serotonin antagonist failed to inhibit cholera toxin-induced jejunal secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Verapamil reversal of serotonin-induced jejunal secretion of water and electrolytes in awake dogs.

Intestinal handling of water and electrolytes was monitored in 5 conscious dogs with chronic 25-cm Thiry-Vella loops of proximal jejunum using a neutral isosmotic perfusate containing [14C]polyethylene glycol as a recovery marker. Under basal conditions the animals absorbed water, Na+, and Cl-, and there was minimal nonsignificant secretion of K+. Intravenous serotonin infusion (30 micrograms/kg X min) increased circulating hormone levels to 937 +/- 131 ng/ml and induced significant secretion of water (-150 +/- 52 microliter/min), Na+ (-22.8 +/- 8.4 microEq/min), Cl- (-23.5 +/- 6.0 microEq/min), and K+ (-1.79 +/- 0.34 microEq/min). Simultaneous infusion of verapamil, a calcium channel blocker, at 8.3 micrograms/kg X min, reversed the intestinal secretion to absorption of all these parameters (144 +/- 32 microliter/min, 15.1 +/- 5.1 microEq/min, 10.3 +/- 3.0 microEq/min, and 0.12 +/- 0.23 microEq/min, respectively). This was accompanied by a significant improvement in the clinical appearance of the animals, decreased visible agitation, and cessation of defecation. Cessation of verapamil infusion (leaving the serotonin infusion unopposed) resulted in prompt return to the secretory state. Serum electrolytes did not change significantly, with the exception of potassium, which fell from 5.1 +/- 0.2 to 4.1 +/- 0.1 mg/dl. In control experiments (no serotonin), verapamil had an insignificant stimulatory effect on the absorption of water, Na+, and Cl- whereas the effect on K+ was significant (-0.2 +/- 0.2 to +0.4 +/- 0.1 microEq/min; p less than 0.05). These data support the role of calcium in modulating the effects of serotonin, and they suggest a new promising technology for the management of serotonin-induced intestinal secretion such as that seen in the carcinoid syndrome.

Animals↗
PubMed1985

Verapamil inhibition of the intestinal effects of substance P.

The undecapeptide substance P (SP) is contained in enterochromaffin cells and circulates in high concentrations in patients with carcinoid syndrome. We have previously reported that elevated SP levels, simulating those reported in patients with carcinoid syndrome, induce profound changes in intestinal water and electrolyte secretion, motility, and blood flow in a canine model. The purpose of this study was to attempt to block the effects of circulating carcinoid levels of SP on intestinal secretion and motility with the calcium channel blocker verapamil. In five dogs a chronic proximal jejunal Thiry-Vella loop was constructed, and after a 2-week recovery the loops were perfused with an isotonic test solution containing 14C-polyethylene glycol as a volume marker. Motor activity was measured by changes in intraluminal pressure and a motility index was calculated with computer-assisted planimetry and expressed as square millimeters per 5 minutes. After a 30-minute baseline period, SP was infused at 50 ng/kg/min for 90 minutes. SP circulating levels rose from a baseline of 6.2 +/- 1.3 pg/ml to a peak of 93.3 +/- 3.1 pg/ml during this infusion. Thirty minutes after the start of this SP infusion, a simultaneous infusion of verapamil (5.0 micrograms/kg/min) was begun at a separate site. During SP infusion there was a significant secretory response of water (-48 +/- 12 microliters/min), Na+ (-7.7 +/- 2.5 microEq/min), Cl- (-8.8 +/- 2.7 microEq/min) and K+ (-0.57 +/- 0.14 microEq/min), and hypermotility (motility index: 1479 +/- 138 mm2/5 min). When verapamil was added a reversal of secretion to net absorption was observed (water: + 116.9 +/- 15.6 microliter/min; Na+: + 13.8 +/- 2.1 microEq/min; Cl-: + 5.5 +/- 2 microEq/min; K+: + 0.38 +/- 0.9 microEq/min) (p less than 0.05). In addition, there was a reduction in motility (motility index: 853 +/- 92 mm2/5 min; p less than 0.05). These results confirm that SP has profound effects on both intestinal motility and secretion and that calcium channel blockade reduces these effects significantly.

Animals↗
PubMed1984

Cholecystitis associated with myelomatosis.

A case of myeloma presenting as acute cholecystitis unresponsive to conventional management is reported. The impairment of the immunological response is a well-known aspect of myeloma, although this usually takes the form of recurrent respiratory infections. It is unusual for acute on chronic cholecystitis, a predominantly Gram-negative infection, to present in this way.

Adult↗
PubMed1982

Bugs and faces in the two visual fields: the analytic/holistic processing dichotomy and task sequencing.

We report three experiments employing outline face and bug stimuli. Subjects either attended to the spatial relationships between and otherwise independent of the individual feature elements (holistic processing condition), or instead attended (with the same stimuli) to the shape of certain discrete feature elements (analytic condition). They were timed in performing discriminatory manual responses to laterally presented targets and nontargets. A left visual field superiority generally occurred under conditions of holistic processing both for faces and bugs, and a right field superiority when analytic processing was required; effects were rather more apparent in the second of a pair of sequential tasks, when the more difficult of the two tasks came first, for the more difficult of the two tasks, and with target rather than, nontarget stimuli. We conclude that those aspects of a stimulus to which a subject is set to attend can determine lateral asymmetries, as well as the actual stimuli themselves, that an analytic/holistic processing distinction is supported, rather than one based on verbal/visuospatial processing, and that task difficulty and order are important variables to be controlled and studied in this context in future research.

Adult↗