From the Institute of Medicine.
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Health Care Reform↗
Biomedical subjects
M Lewin
Publications and source records attributed to M Lewin.
Continuous ambulatory peritoneal dialysis as the primary approach in the management of severe renal insufficiency in pregnancy.
Pregnancy is an unusual event in patients with chronic renal failure undergoing dialysis. The outcome in these cases is usually poor. We report a pregnancy complicated by severe renal insufficiency that was managed successfully by continuous ambulatory peritoneal dialysis. Dialysis was initiated at 24 weeks' gestation. At 34 weeks, premature labor associated with peritonitis resulted in the spontaneous delivery of a healthy male infant weighing 2400 g. The use of continuous ambulatory peritoneal dialysis during pregnancy offers theoretical advantages compared with hemodialysis. Our case, added to the available limited experience with this new modality, suggests that it may be an appropriate approach in women developing renal disease for the first time during pregnancy.
Adult↗
Paf-acether synthesis by Helicobacter pylori.
Clinical studies suggest that Helicobacter pylori may play a role in the pathogenesis of gastroduodenal ulcers in man but direct evidence of mucosal injury by this microorganism is still lacking. Paf-acether (paf) causes a number of disorders including ischaemic bowel necrosis and gastroduodenal ulceration. Since paf is produced by Escherichia coli, we investigated whether it could be synthesised by H pylori. Five H pylori isolates were collected from antral biopsy specimens from patients with gastritis and duodenal ulcer and cultured with selective antibiotics. Colonies obtained from both blood agar and brucella broth medium were used. Paf was determined by platelet aggregation assay after ethanolic extraction and subsequent purification by high performance liquid chromatography. Paf was detected in H pylori in blood agar plates (680 (390) pg paf/1 x 10(6) organisms) but not in bacteria cultured on brucella broth medium. Supplementation of the latter medium with lyso paf and acetyl-CoA, two paf precursors present in high amounts in the mammalian intestine, induced paf production in three of five isolates. The platelet aggregating material extracted from H pylori exhibited biological and physiochemical characteristics identical to those of paf released from eukaryotic cells. These findings suggest that H pylori may add to the local production of paf in inflamed gastric mucosa.
Bacteriological Techniques↗
The influence of spontaneous accelerations of fetal heart rate on umbilical artery velocity waveforms.
For clinical interpretation of Doppler waveforms, it is important to establish the extent to which fetal heart rate changes affect the umbilical artery velocity waveform. Umbilical artery waveforms were measured with continuous wave ultrasonography during spontaneous accelerations of the fetal heart rate in 20 uncomplicated, near-term pregnancies. On average, an acceleration of 20 beats/min of fetal heart rate within an individual was associated with a reduction in the systolic/diastolic velocity ratio of 0.25. There was, however, considerable variability in the response, and in six patients the systolic/diastolic ratio actually increased with heart rate. We conclude that fetal heart accelerations within the normal range cause only small and variable changes in the systolic/diastolic ratio.
Blood Flow Velocity↗
A noise-free molecular hybridization procedure for measuring RNA in cell lysates.
A solution hybridization technique was designed to measure RNA abundance in crude cell lysates and at the same time to maximize confidence that signals resulted from true molecular hybridization. Cell lysates were prepared in 5 M guanidine thiocyanate, then RNA molecules in the lysates were hybridized with two probes, a 32P-labeled RNA "label probe" which provided signal and an oligodeoxyribonucleotide "capture probe" containing a poly(dA) tail which provided a mechanism for selective purification. Ternary hybrids were "captured" on oligo(dT)-coated superparamagnetic beads through a readily reversible interaction with the poly(dA) of the capture probe. RNA did not bind to dT beads through poly(A) under the capture conditions used. Hybrids were purified through cycles of capture on and release from dT beads, with each cycle yielding a 100- to 1000-fold reduction in noise (unhybridized label probe) and a 50-90% recovery of signal (hybridized label probe). Noise was driven below detectable limits after three cycles of capture, thereby improving the sensitivity of measuring target RNA. As few as 15,000 target molecules, 15 fg of a 3-kb RNA, was detectable in the equivalent of 2 x 10(6) cells in concentrated cell lysates (10(8) cells/ml). Since hybridization with both probes was required in order to yield a signal, hybridization specificity could be adjusted with either or both probes. The greater specificity and lack of noise increased confidence that the signal was proportional to the amount of RNA of interest.
Guanidines↗
Clinical, immunological, and virological effects of ampligen, a mismatched double-stranded RNA, in patients with AIDS or AIDS-related complex.
10 patients with the acquired immunodeficiency syndrome (AIDS), AIDS-related complex (ARC), or lymphadenopathy syndrome (LAS) were given 200-250 mg ampligen, a mismatched double-stranded (ds) RNA with in-vitro antiviral activity against human immunodeficiency virus (HIV), twice a week for up to 18 weeks, without side-effects or toxicity. In all 9 patients who were positive for HIV RNA in peripheral blood mononuclear cells before therapy, levels became undetectable between days 10 and 40 of the start of therapy. 6 of the 7 patients with ARC or LAS also showed a progressive reduction in HIV load as measured by co-culture assays. All 10 patients had augmentation of delayed-type hypersensitivity skin reactions. Other changes noted during ampligen therapy included an increase in or maintenance of numbers of helper-inducer T lymphocytes, improvements in HIV-related symptoms, rises in titre of neutralising antibodies against HIV, and restoration of proper functioning of the natural lymphocyte antiviral dsRNA-dependent (2'-5'-oligoadenylate/RNA-ase L) pathway. Thus, in the short term, ampligen seems to have the dual ability to restore immunological function and to control HIV replication.
AIDS-Related Complex↗
Intestinal transit of food after total gastrectomy and Roux-Y esophagojejunostomy.
We examined small bowel transit of solid food in 10 patients 3 to 30 months after total gastrectomy and Roux-Y esophagojejunostomy and compared the transit pattern with that in five control subjects. All persons ate a test meal consisting of 213 g of beef stew mixed with 30 g of chicken liver which was labeled with 1 mCi of technetium 99m sulfur colloid, and they stood in front of a gamma scintillation camera and were studied for 6 to 10 hours. Solid food passed rapidly from the esophagus through the Roux-Y limb and became uniformly distributed throughout a long segment of the small intestine. Mouth-to-colon transit time was 223 +/- 18 minutes in the control subjects and 298 +/- 37 minutes in the patients with gastrectomy. Small bowel transit of the head of the meal was 187 +/- 19 minutes in the control subjects and 293 +/- 37 minutes in the patients (p less than 0.02). Transit time of the tail of the meal was 175 +/- 26 minutes in the control subjects and 396 +/- 28 minutes in the patients (p less than 0.001). After total gastrectomy and Roux-Y esophagojejunostomy, the proximal jejunum does not act as a reservoir; transit of food through the small intestine is slower than in control subjects, and because the proximal jejunum empties rapidly during eating, a meal of normal size can be consumed. These findings do not support the idea that an artificial gastric reservoir is important after total gastrectomy.
Adult↗
Solubilization and reconstitution of the gastric H,K-ATPase.
Proteoliposomes containing the hog gastric H+,K+-ATPase were prepared from cholate and n-octyl glucoside extracts of native microsomes. Experiments were presented which show reconstitution-dependent selective purification of a 94-kDa peptide capable of Rb+/Rb+ exchange and active H+ transport. The absence of selective enrichment of residual protein contamination in this material suggests but does not prove that those transport reactions are attributable only to the 94-kDa peptide. Transport demonstrated inhibitor sensitivity and cation specificity comparable to the microsomal gastric ATPase. In K2SO4 media the H+ transport reaction was protonophore insensitive and correlated with MgATP-dependent 86Rb+ extrusion. This and other evidence suggested that active transport occurs via electroneutral H+in for K+out exchange. 86Rb+ exchange (uptake) in the proteoliposomes demonstrated both saturable and nonsaturable components. At a K0.5 = 1.5 mM, saturable 86Rb+ uptake accounted for about 90% of Rb+ influx. The vanadate-sensitive cation exchange indicated that the ATPase was reconstituted asymmetrically into the proteoliposomes (70% cis-/30% trans-vanadate site). 86Rb+ exchange was inhibited by ATP and stimulated about 2-fold by low Mg2+ and 5 mM phosphate. These ligand effects and the demonstration of comparable rates of passive exchange and active Rb+ efflux suggest that passive K+ exchange is not severely limited by a K+-occluded enzyme form in the H,K-ATPase. A model compatible with this hypothesis is suggested.
Adenosine Triphosphatases↗
Alkaline reflux gastritis and the effect of biliary diversion on gastric emptying of solid food.
We prospectively studied 15 consecutive patients treated for alkaline reflux gastritis to determine the gastric motility pattern associated with this disease and the effects of Roux-Y gastrojejunostomy on gastric emptying. Eleven patients had previous antrectomies (the Billroth I procedure in 4 and the Billroth II procedure in 7), and 4 had previous cholecystectomies. Gastric emptying was measured before and after Roux-Y reconstruction by computer analysis of data from a scintillation camera using technetium 99m tagged chicken liver mixed with beef stew. Gastric emptying was also measured in another 10 patients who had previous Roux-Y gastrojejunostomies and were thought from clinical findings to have gastroparesis. In the patients with alkaline gastritis, before surgery gastric emptying was normal in 25 percent, rapid in 45 percent, and delayed in 30 percent. After Roux-Y reconstruction, the rate of gastric emptying increased in 25 percent of patients, decreased in 45 percent, and did not change in 30 percent. Gastric bezoars developed in half of the patients whose gastric emptying decreased after surgery. There were no technical features of the operations nor mechanical abnormalities of the reconstructions that characterized the patients whose gastric emptying slowed postoperatively. Forty percent of the patients studied only after Roux-Y reconstruction had rapid gastric emptying, 30 percent had normal gastric emptying, and 30 percent had delayed gastric emptying. These data show that patients with alkaline reflux gastritis do not have a single pattern of gastric emptying, and Roux-Y reconstruction has no consistent effect on gastric emptying.
Adult↗
Gallbladder filling and response to cholecystokinin are not affected by vagotomy.
We studied the effects of vagotomy on gallbladder (GB) motility in prairie dogs and humans with infusion cholescintigraphy. Twelve male prairie dogs were anesthetized and given an intravenous infusion of 120 microCi of diethyl-HIDA for 150 minutes. Images were acquired every 10 minutes. Then cholecystokinin (CCK)-8, 1.5 micrograms/kg, was given as a bolus, and images were acquired for another 30 minutes. We repeated the studies giving 300 micrograms/kg of atropine 20 minutes before administration of CCK-8. All animals underwent truncal vagotomy, and the studies were repeated 1 and 3 months later. The GB filled in a stepwise fashion; partitioning of bile varied from one 10-minute period to the next and averaged 20% +/- 2%/80% +/- 3% during the 150-minute period. Episodic partial GB emptying (ejection fraction 19% +/- 2%; intervals of 70 +/- 5 minutes) occurred during this phase. GB filling and partitioning of bile were unchanged after vagotomy. GB ejection fraction in response to CCK-8 was 69% +/- 6% in controls, 74% +/- 5% after atropine, 78% +/- 8% 4 weeks after vagotomy, and 66% +/- 6% 3 months after vagotomy. Sixteen human subjects were studied after parietal cell vagotomy (six patients) or truncal vagotomy and drainage (10 patients). GB filling average 2.5% +/- 2% per minute in patients who underwent truncal vagotomy and 3% +/- 1% per minute in patients who underwent parietal cell vagotomy. GB emptying in response to CCK-33 (0.02 U/kg/min) was 74% +/- 7% in patients who underwent truncal vagotomy and 82% +/- 4% in patients who underwent parietal cell vagotomy. Thus neither GB filling nor GB emptying in response to CCK was altered by cholinergic blockade or vagotomy.
Animals↗
Optimizing metoclopramide control of cisplatin-induced emesis.
Using an original high-pressure liquid chromatographic assay, we measured serum levels of metoclopramide and defined a concentration-response relationship for metoclopramide control of cisplatin-induced emesis. Using a metoclopramide regimen of 2 mg/kg body weight intravenously every 2 hours for four doses, we found that serum levels greater than 850 ng/mL immediately before the third dose were associated with complete control of emesis (less than three episodes) in 78% of patients and partial control (three to five episodes) in 18%. No patient with levels less than 850 ng/mL had complete control of emesis; only 42% had partial control (p less than 0.001). Increases in dosage for patients with low levels and poor responses improved control in four of five patients. Elderly patients had drug levels similar to those of young patients but had fewer episodes of emesis (p = 0.044), suggesting that elderly patients have increased sensitivity to this drug. The metoclopramide dose can be raised up to 2.75 mg/kg with an improvement in emetic control in patients who have an inadequate response to doses of 2 mg/kg and no toxicity.
Adult↗
Metoclopramide and chemotherapy-induced emesis.
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Antineoplastic Agents↗
[Roles of cyclic AMP and calcium in the mechanism of the release of growth hormone by somatocrinin].
Growth hormone (GH) release from Rat pituitary cell monolayers in response to synthetic somatocrinin (7.8 to 1,000 pmol/l) is paralleled with an increase in cellular cyclic AMP (cAMP) content and efflux of cAMP in the extracellular medium. Somatostatin and blockers of calcium-dependent cellular mechanisms inhibit somatocrinin-induced GH release but only partially decrease (somatostatin, CoCl2) or even increase (trifluoperazine) cAMP levels. Thus, calcium is required for somatocrinin action and GH release is not simply dependent on stimulation of cAMP metabolism.
Animals↗
Playing the game-for keeps.
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Career Mobility↗
Childhood dermatitis herpetiformis. Review of the new aspects and report of a case.
Dermatitis herpetiformis (DH) of linear IgA type occurred in a 6-month-old boy shortly after initiating sulfisoxazole therapy for a urinary tract infection. Generalized pruritic bullae on erythematous bases were present on his trunk and extremities. There were no clinical or laboratory findings suggestive of gastrointestinal involvement. Direct immunofluorescent studies of skin biopsies taken early in the course of the disease and while the child was on systemic corticosteroid therapy were negative. Eventually a linear deposition of IgA at the dermoepidermal junction of involved skin on direct immunofluorescence was demonstrated. No circulating antibodies to the basement membrane were found. Because of close proximity of the initiation of sulfisoxazole (Gantrisin) therapy and the eruption of the initial bullous lesions, this case also presents an interesting diagnostic and therapeutic problem. Negative assays of lymphocyte migration inhibition factor (LMIF) to sulfisoxazole indicated that the likelihood of a hypersensitivity reaction to sulfa drugs was slight. The patient's clinical response to dapsone therapy was dramatic. The conflicting views of subepidermal bullous dermatosis of childhood and the difficulties in confirming a diagnosis of DH are discussed. We contend that when DH is suspected in children, various laboratory tests should be repeated several times before the diagnosis can be confirmed. The case presented here is the youngest child reported with this type of DH.
Dapsone↗
[Food antibodies in immunofluorescence in various disorders of gastrointestinal metabolism of food antigens].
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Antibodies↗
Dietary cholesterol is co-carcinogenic for human colon cancer.
Colorectal carcinoma is becoming the most common form of visceral cancer in Western populations. A fat-related dietary factor is implicated in its pathogenesis, and evidence in man suggests that this factor may be cholesterol. Dietary cholesterol is co-carcinogenic in animals with colon cancer, and there is indirect evidence for a similar role in man. It is proposed that prolonged exposure to dietary cholesterol is co-carcinogenic for human colon cancer in that it facilitates the development, growth, and spread of this disease.
Animals↗