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Biomedical subjects

S Hurwitz

Publications and source records attributed to S Hurwitz.

At least 145 records · Page 8Linked to original sources

Final report of the phase I trial of single-dose WR-2721 [S-2-(3-aminopropylamino)ethylphosphorothioic acid].

Two hundred one patients were entered in a single-dose phase I trial of WR-2721 [S-2-(3-aminopropylamino)ethylphosphorothioic acid]. Major toxic effects included emesis and hypotension. The observed minor toxic effects were somnolence and sneezing. Two infusion schedules were tested: long-infusion time, which fixed the rate, but varied total time; and short-infusion time, which varied the rate, but fixed the time to 15 minutes. Emesis was significantly influenced by infusion time; the long schedule caused a 57% incidence whereas the short schedule caused only a 28% incidence. Within the long-infusion group, higher-dose patients and women were more likely to vomit. Although only 15% of the entire group had hypotension, the long-infusion schedule had a hypotension incidence of 23%; the short schedule had an incidence of only 3% (P less than 0.0005). Within the long-infusion group, dose and tumor site significantly influenced the incidence of hypotension. No factors were associated with these toxic effects in the short-infusion schedule. However, certain toxic effects were too infrequent to detect significant differences. For future trials we recommend 740 mg/m2 infused in 15 minutes. With this schedule, vomiting was seen in 25% of infusions and hypotension was seen in only one of 68 infusions. To date, no delayed toxic effects have been detected in any organ system, and the trial resulted in no toxic deaths.

Adult↗

The role of lymph node dissection for clinical stage I malignant melanoma of intermediate thickness (1.51-3.99 mm).

The survival times of patients who had an elective regional lymph node dissection was compared with that of those who did not undergo the procedure in a database of 72 patients with clinical Stage I melanoma of intermediate thickness (1.51-3.99 mm). All of the patients had been followed for 5 years or longer or until death. No significant differences were found in other reported prognostic factors, suggesting that the two groups were comparable. By multivariate analysis, a low mitotic rate, intermediate patient age, and the presence of an infiltrative lymphocytic response were found to be associated with favorable survival. There did not appear to be any association of elective regional lymph node dissection with survival; and it was concluded that such therapy should not be regarded as "standard" for clinical Stage I melanoma of intermediate thickness.

Actuarial Analysis↗

Discriminant scorecard for diagnosis of invasive pulmonary aspergillosis in patients with acute leukemia.

Invasive pulmonary aspergillosis, a serious opportunistic infection in adult patients with acute leukemia, is difficult to diagnose antemortem. To identify patients with invasive pulmonary aspergillosis without reliance on invasive diagnostic procedures, a discriminant scorecard for invasive pulmonary aspergillosis based on clinical parameters was evaluated in a three-phase study. In phase I, the records of 62 patients, including 15 with invasive pulmonary aspergillosis, were reviewed. Eleven clinical parameters distinguished patients with invasive pulmonary aspergillosis from control subjects. These parameters were combined into a discriminant scorecard. In phase II, the discriminant scorecard was validated by a blinded, retrospective review of 94 consecutive admissions. The discriminant scorecard score was highly associated with the clinical outcome (p less than 0.0005). The sensitivity of the discriminant scorecard was calculated as a range from 62.9 to 92.8 percent and the specificity as a range from 87.5 to 98.3 percent. In phase III, the clinical utility of the discriminant scorecard was determined by its prospective application to 49 consecutive patient admissions. The discriminant scorecard identified patients with invasive pulmonary aspergillosis at an average of 4.1 days prior to clinical recognition of the disease and initiation of amphotericin B therapy. The discriminant scorecard outperformed a complex function based on multiple linear regressions, was easy to use, and did not require difficult calculations. Thus, for this patient population, the discriminant scorecard was an accurate, useful noninvasive screening test for invasive pulmonary aspergillosis. The scorecard allows more rapid clinical identification of patients with this infection and could lead to improved patient survival through earlier diagnostic and therapeutic intervention.

Acute Disease↗

Metabolism and motility of turkey (Meleagris gallopavo) spermatozoa in the presence or absence of oxygen, glucose and fructose.

Sugar consumption by turkey spermatozoa for 1 hr at 37 degrees C was similar in the presence or absence of oxygen, and with glucose or fructose in the medium. Motility of the spermatozoa at the end of the above incubation period was lower under anaerobic than aerobic conditions. Fructose enhanced the oxygen uptake of spermatozoa in comparison with that in the glucose-containing medium. Omission of sugar from the medium depressed respiration but not motility of the spermatozoa. The rate of oxygen uptake by the spermatozoa during a 3-hr incubation period was higher in a 3.3-mM than a 15.0-mM glucose medium. Fructose was formed from glucose under aerobic but not under anaerobic conditions. Fructose originating from glucose was used for fructolysis, when the glucose reserve in the medium was almost exhausted.

Aerobiosis↗

High-dose oral metoclopramide. An effective antiemetic agent.

Seventy-six patients receiving cisplatin and noncisplatin-containing cancer chemotherapy were treated with an outpatient phase II metoclopramide regimen. The program consisted of an outpatient intravenous loading dose of metoclopramide before chemotherapy, followed by oral metoclopramide at 1, 3, 5, and 8 hours after chemotherapy. Three oral dose levels were evaluated. Treatment with 2 mg/kg/dose or 100 mg/dose resulted in no vomiting in 53% of 65 evaluable patients, and 0-2 episodes of emesis in 74%. Oral doses of 50 mg/dose were less effective, preventing emesis in 18%. This trial demonstrated the antiemetic effectiveness of high-dose oral metoclopramide in a new schedule designed for the outpatient setting. The side effects included restlessness (51% of patients), dystonic reactions (9%), and gastrointestinal complaints (41%).

Adolescent↗

Erythema chronicum migrans and Lyme disease.

Lyme disease is an inflammatory disorder with a wide spectrum of clinical manifestations that involve the skin, joints, heart, and nervous system (1-4). Initially described in 1977 and named after the rural town in Connecticut where the first cases were detected in 1975, Lyme disease has now been recognized in at least 24 states (5-7), Canada (8), Australia (9), France (10), Switzerland (11), and Germany (12), and in individuals who travel to or spend time in areas known to be endemic for this disorder (13).

Adult↗

Invasive pulmonary aspergillosis in adult acute leukemia: clinical clues to its diagnosis.

Invasive pulmonary aspergillosis, a leading cause of morbidity and mortality in patients with acute leukemia, is difficult to diagnose antemortem because its signs and symptoms are ill-defined. To refine the clinical description of this infection, we reviewed our experience with 15 pathologically documented cases of invasive pulmonary aspergillosis in a population of 60 patients treated for acute leukemia. Findings occurring significantly more often (P less than or equal to .001) among cases than controls included pleuritic chest pain; acute sinus tenderness, and nasal discharge, epistaxis and eschar; rales; development of multilobar infiltrates after the 14th hospital day; and presence of nodular or cavitary infiltrates. In addition, patients with invasive pulmonary aspergillosis had a significantly prolonged duration of granulocytopenia, more febrile days and febrile episodes without a fever diagnosis and more febrile days on antibiotics (P less than or equal to .001 in all). This complex of findings should improve the clinician's ability to diagnose invasive pulmonary aspergillosis in patients with acute leukemia.

Acute Disease↗

Movement and absorption of major minerals and water in ovine gastrointestinal tract.

Movement of calcium, chloride, magnesium, potassium, sodium, and water in the intestine of sheep was determined with cerium-141 as an unabsorbed reference substance. Net secretion of phosphorus and sodium, but not of potassium and calcium, was observed to the rumen. Water disappeared from the omasum and was secreted in the abomasum. Chloride secretion occurred in the omasum and more in the abomasum. Extensive secretion in the duodenum increased flows of sodium and potassium 8 to 9 times; of calcium, chloride, and phosphorus 3 to 6 times; of magnesium 1.3 times; and of water 12 times. Reabsorption was rapid in the small intestine, the major site of disappearance of all ions. Rates of disappearance decreased with increasing distance from the pylorus. Little further net disappearance of calcium, phosphorus, magnesium, or potassium was found in the large intestine, whereas water, sodium, and chloride disappearance continued. Overall absorption of sodium, potassium, and chloride was approximately 90%, of phosphorus 63%, of calcium 38%, and of magnesium 71%. This study highlights the importance of endogenous secretions in mineral absorption in the sheep.

Animals↗

Isolation and purification of avian parathyroid hormone using high performance liquid chromatography, and some of its properties.

A peptide has been extracted in acetic acid from the parathyroid glands of chicks (Gallus domesticus) raised on a vitamin D-deficient diet. The peptide was purified by gel filtration and high-performance liquid chromatography (HPLC). Its degree of purity was ascertained also by SDS-polyacrylamide gel electrophoresis. The avian hormone had the same SDS electrophoretic mobility as bovine parathyroid hormone (bPTH) and therefore a similar molecular weight. The avian peptide was lower than bPTH in basic amino acids and considerably higher in glycine. Evidence for the identity of the peptide as avian parathyroid hormone relies on its source, the similarity of its molecular weight to that of bPTH, and its high potency in stimulating cyclic AMP production in kidney cells in vitro and in vivo.

Animals↗

Intestinal absorption and plasma transport of lipids in chicks and rats.

Labelled oleic acid was introduced into the duodenum of chicks in which the pancreatic-duodenal vein and brachial artery had been cannulated, and blood samples were withdrawn. Similar experiments were performed in rats which had not been venously cannulated. In rat plasma, over 92% of the label was found in the triglycerides, whereas in the chick 64% of the label was in the triglycerides and 27-31% in the free fatty acids. In the rat, over 85% of the lipid label circulating in the plasma was found in lipoproteins with hydrated density less than 1.006, whereas in the chick only 25% of the label was in this fraction and the majority of label was found with density greater than 1.063. It thus appears that both release and transport of fatty acids from the intestinal mucosa in chicks differs from the rat.

Animals↗

The lack of relationships between vitamin D3 metabolites and calcium-binding protein in the eggshell gland of laying birds.

The relationship of the metabolism of vitamin D3 and calcium-binding protein (CaBP) to calcium transport by the eggshell gland (ESG) was assessed in chickens. Plasma or ESG 1,25 dihydroxyvitamin D3 (1,25(OH)2D3) and ESG CaBP were no different between periods of ESG inactivity and of shell calcification. A severe dietary calcium deficiency resulted in increased kidney 25-hydroxycholecalciferol-1-hydroxylase activity (542%), plasma and ESG 1,25(OH)2D3 concentrations (193 and 274%, respectively), but in decreased ESG CaBP (34%), associated with the production of poorly calcified eggs. Significant correlations were found between 25 hydroxycholecalciferol-1-hydroxylase, plasma 1,25(OH)2D3 and ESG 1,25(OH)2D3, but not between ESG 1,25(OH)2D3 and CaBP. Hens with a low shell density had a significantly lower (55%) ESG CaBP than those with high shell density, without any significant change in ESG 1,25(OH)2D3. Significant correlations were found between ESG CaBP and shell calcium. Total receptors for 1,25(OH)2D3 were lower in ESG than in the intestine. The results suggest that CaBP level and calcium transport in the ESG are not regulated by 1,25(OH)2D3.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗

Both cholera toxin-induced adenylate cyclase activation and cholera toxin biological activity are inhibited by antibodies against related synthetic peptides.

The immune response against six synthetic peptides corresponding to various segments of the B subunit of cholera toxin was evaluated. Conjugates in which the peptides were covalently linked to tetanus toxoid served for immunization of rabbits. As previously reported, four of these conjugates elicited antibodies cross-reactive with intact cholera toxin. We report here that antisera against two of these synthetic peptides inhibit the entire spectrum of activities of the intact cholera toxin. This is manifested both on the biochemical level (adenylate cyclase induction) and on the biological effect (intestinal fluid secretion). These results indicate that these peptides may serve as suitable candidates for preparation of a synthetic anticholera vaccine.

Adenylyl Cyclases↗

Calcium metabolism in birds: computer simulation of response to 1,25-dihydroxycholecalciferol.

A simulation model of calcium metabolism in the chick has been used to evaluate the response of the systems that regulate plasma calcium to a continuous input of 1,25-dihydroxycholecalciferol [1,25(OH)2D3] from the intestine. The results of simulation showed that the concentration of the vitamin D metabolite in the intestine increased during the first 24 h and thereafter decreased slightly due to suppression of endogenous hormone production. Metabolite accumulation was accompanied by an increase in calcium absorption, with a lag period of about 4 h. Most of the increase in absorbed calcium was excreted in the urine, with a lesser change in net bone calcium uptake. Plasma calcium increased with time, in proportion to the intake of the exogenous hormone. The validity of the predicted steady-state plasma calcium levels, and bone and kidney calcium flows, is discussed. The results of the simulation demonstrate the importance of the vitamin D-intestinal axis in regulation of plasma calcium.

Animals↗

Identification of early relapsing patients with adult acute nonlymphocytic leukemia by bone marrow biopsy after initial induction chemotherapy.

Bone marrow biopsies obtained from 69 adult patients with acute nonlymphocytic leukemia (ANLL) six to 10 days after initial induction chemotherapy were reviewed blindly to detect the presence of residual leukemia. Discrimination between the presence or absence of leukemic cells was provided by assessment of the numbers, clustering, and nuclear morphology of blasts and promyelocytes. Twenty-six patients had frank leukemia, 25 had no apparent leukemic cells, and 18 had focal residual leukemia. Of 25 patients whose bone marrow contained no detectable residual leukemic cells, 21 gained complete remission without further chemotherapy. These patients had a median duration of remission of 278 days, with five patients still remaining in remission for 578-882 days. Similarly, all of the 18 patients who had focal residual leukemia achieved complete remission without additional chemotherapy; however, all have relapsed with a median duration of remission of 163 days. This study indicates that patients with foci of residual leukemia in their one-week posttreatment bone marrow samples readily achieve remission, but carry a substantial leukemic burden that increases the likelihood of early relapse.

Acute Disease↗

Effect of pH on the metabolism and fertility of turkey spermatozoa.

Oxygen uptake during a 4-h incubation period at 37 degrees C, and the motility of the spermatozoa before and after incubation, increased significantly with increasing pH from 6.3 to 8.8. No interaction between buffer and pH was noticed. In a second series of experiments on the aerobic metabolism of turkey spermatozoa, the effect of the pHs 6.8, 7.3 and 7.8 was studied. Fructose was formed from glucose without regard to the pH of the medium. The glucose consumption, i.e. the glucose disappearance minus fructose formation, the lactic acid accumulation, and the oxidation of glucose and of other substances, were higher, although not always statistically, at pH 7.8 than at pH 6.8. The percentage of fertile eggs during the 3rd week of collection after insemination with fresh semen diluted in the pH 7.8 medium was significantly lower than that with semen diluted in the pH 6.8 or 7.3 media. After 4 h of storage at 15 degrees C, the decrease in the fertility of spermatozoa in the high pH medium was apparent from the 1st week of collection.

Animals↗

Egg shell quality, medullary bone ash, intestinal calcium and phosphorus absorption, and calcium-binding protein in phosphorus-deficient hens.

The effect of dietary phosphorus deficiency on the performance and on various parameters of calcium, phosphorus, and vitamin D metabolism was studied in laying hens. Phosphorus deficiency resulted in a decline in rate of production and egg weight, probably through appetite depression. The latter, or any secondary calcium deficiency, does not appear to cause the observed reduction in shell quality due to the deficiency. Similar to the response in the chick, phosphorus deficiency resulted in an increase in calcium-binding protein in intestine and kidney, there was no change in the activity of kidney 25-hydroxy-vitamin D3-1-hydroxylase. Percentages of calcium and phosphorus absorption were also higher during phosphorus deficiency. Medullary bone ash, decreased during phosphorus deficiency, was probably due to a reduction in the rate of bone formation.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗