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Biomedical subjects

A Greene

Publications and source records attributed to A Greene.

At least 19 recordsLinked to original sources

Effect of comprehensive intervention program on survival of patients with human immunodeficiency virus infection.

BACKGROUND: In October 1989, an early intervention program (EIP) for human immunodeficiency virus (HIV) infection was initiated in New Jersey to provide medical care and social services to the enrollees. OBJECTIVE: To assess the overall effect of the EIP on the survival of HIV-infected patients. METHODS: Patient information collected through June 30, 1993, was analyzed from the Jersey City Medical Center EIP clinic. Survival from enrollment to death was calculated for patients who received follow-up at the clinic (active) and for those who only had the enrollment visit (inactive). The data were matched with the New Jersey death certificate registry. RESULTS: Of 938 patients enrolled from October 1989 to December 1991, 767 had T-cell subsets determined within 3 months of enrollment: 641 patients were active and 126 were inactive. At entry, inactive patients had a lower median CD4+ T-cell count and were more likely to be symptomatic than active patients. Among the 640 active and 125 inactive patients analyzed for survival (survivors > or = 2 months), there were 144 (22.5%) and 48 (38.4%) deaths, respectively. Kaplan-Meier analysis indicated longer survival for active patients than for inactive patients (P < .001, Wilcoxon's test for homogeneity of strata); eg, survival probability at 2 years was 86% for active patients and 64% for inactive patients. Active patients also had longer survival than inactive patients when stratified by CD4+ T-cell levels or by clinical status. Only active and inactive patients with both CD4+ T-cell levels lower than 0.20 x 10(9)/L (< 200/microL) and symptoms of HIV or acquired immunodeficiency syndrome had similar survival rates. Survival was not influenced by sex, race, or HIV transmission category. CONCLUSION: Participation in the EIP was associated with longer survival of HIV-infected patients.

Adolescent

Conditional differentiation of heart- and smooth muscle-derived cells transformed by a temperature-sensitive mutant of SV40 T antigen.

To create muscle cell lines that conditionally differentiate in vitro we introduced a temperature-sensitive SV40 T antigen by retroviral infection into rat aortic smooth muscle cells (SMCs) and neonatal heart-derived cells. After G418 selection cell lines isolated were characterized at permissive (33 degrees C) and non-permissive (39 degrees C) temperatures. [3H]Thymidine uptake showed tht progression through the cell cycle is greatly reduced at 39 degrees C. Cytoskeletal proteins, such as actins and vimentin did not change significantly after temperature shift, while the number of desmin-positive SMCs significantly increased when cells were switched to 39 degrees C. Heart-derived muscle cells showed sarcomeric myosin heavy chain reactivity only when grown at 39 degrees C. After thrombin stimulation intracellular calcium in both cell types increased severalfold in 39 degrees C-cells but not in 33 degrees C-cells. Whole cell patch-clamp recordings of SMCs and heart-derived cells revealed a strong increase in nicardipine-sensitive Ca2+ current when cells were switched to 39 degrees C. Nicardipine-insensitive Ca2+ current also increased in both cell types at the non-permissive temperature. Na+ current in SMCs was large at 33 degrees C and small or not detectable at 39 degrees C and absent in heart-derived cells. Using a cDNA probe specific for the alpha 1 subunit of the dihydropyridine-sensitive Ca2+ channel we demonstrate a temperature-sensitive expression of the dihydropyridine receptor mRNA in smooth muscle-derived cells but not in heart-derived H10 cells. Our results suggest that upon downregulation of SV40 T antigen these cells become quiescent and exhibit a more differentiated phenotype. These cell lines may provide a useful tool to investigate ion channel- and receptor signal transduction, as well as cell cycle control in smooth and possibly cardiac muscle cell differentiation.

Animals

Generic engineering.

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Hospital Restructuring

Repair for a broken market: the medical service company.

Sky-rocketing costs are fueling debate over whether market mechanisms can work for the healthcare services industry. The market for health care certainly seems to be broken. Value is decreasing, services are fragmented and costly transactions among providers are exacting a great toll in efficiency and service. Perhaps ironically, this situation presents a golden opportunity for providers who understand that the market is merely responding to the combined stimuli of inflated demand and excessive regulation. We believe that Medical Service Companies, which unite physicians and hospitals under one corporate roof, can reduce market friction, improve the responsiveness of providers and provide better value than traditional provider organizations.

Cost-Benefit Analysis

Sequential Tc 99m mercaptoacetyl-triglycine (MAG3) renography as an evaluator of early renal transplant function.

A prospective study was carried out to evaluate the role of sequential Tc 99m MAG3 renography in assessing transplant function in the early post-operative period. Twenty patients were included in the study. Studies were performed on all patients at intervals of 48-72 hours until discharge. There were 11 clinically diagnosed episodes of rejection, 9 of which were correctly diagnosed using MAG3 renography. Six episodes of rejection were diagnosed prior to the onset of clinical symptoms. Two patients with graft infarction were correctly diagnosed. Six patients had evidence of transient renographic abnormalities in the immediate post-operative phase which were not associated with clinical symptoms, all of these resolved spontaneously on subsequent examinations and were presumed to be related to resolving acute tubular necrosis (ATN). The perfusion index was of no discriminatory value in this study. Sequential Tc 99m MAG3 renography is highly sensitive but entirely nonspecific in the evaluation of pathology in the transplant kidney. Rejection in an uncomplicated transplant can be readily detected in many cases well in advance of clinical manifestations. This study demonstrates that Tc 99m MAG3 renography is certainly equal to Tc 99m DTPA renography or Iodine 131 renography in assessing early transplant function. However, Tc 9m MAG3 exposes the patient to considerably less radiation and the images are of superior quality.

Adolescent

Comparison of topical tetracaine, adrenaline, and cocaine anesthesia with lidocaine infiltration for repair of lacerations in children.

Local anesthetic infiltration is painful and frightening for children. We prospectively compared a topical alternative, TAC solution (tetracaine 0.5%, adrenaline 1:2,000, cocaine 11.8%), with 1% lidocaine infiltration for use in laceration repair in 467 children. Adequate anesthesia of facial and scalp wounds was achieved for 81% of TAC-treated wounds versus 87% of lidocaine-treated wounds (P = .005). TAC was less effective on extremity wounds; 43% had effective anesthesia compared with 89% of lidocaine-treated extremity wounds (P less than .0001). No systemic toxicity was observed. The incidence of wound infection was 2.2% for both TAC and lidocaine. Wound dehiscence occurred in seven TAC- and two lidocaine-treated facial or scalp wounds (4.5% vs 1.8%, NS) and in five TAC- and four lidocaine-treated extremity wounds (20% vs 17.4%, NS). The unusually high rate of dehiscence was due partially to recurrent trauma or coincident infection. TAC was well accepted by patients and parents. We encourage the careful use of TAC as a less painful alternative to lidocaine infiltration for selected scalp and facial lacerations in children.

Administration, Topical

Tissue specificity, localization in brain, and cell-free translation of mRNA encoding the A3 isoform of Na+,K+-ATPase.

The isolation of multiple Na+,K+-ATPase cDNAs from rat brain has led to the discovery of a family of alpha-isoform genes. Using A1 (alpha), A2 (alpha+), and A3 (alpha III) Na+,K+-ATPase gene probes, we have analyzed the distribution of Na+,K+-ATPase mRNAs in adult and fetal rat tissues by RNA blot and hybridization histochemistry. A1 Na+,K+-ATPase mRNA was found ubiquitously among various tissues, with highest levels in transport epithelial and neural tissues. A2 mRNA was found in adult neural and muscle tissues, and A3 mRNA was found only in neural tissues and fetal heart muscle. Both A1 and A2 mRNAs were less abundant in fetal brain than in adult brain; in contrast, A3 mRNA was abundant at both stages. In situ mapping of brain areas that contain A3 mRNA suggests that this Na+,K+-ATPase isoenzyme is expressed predominantly by neural cells. Analysis of Na+,K+-ATPase proteins generated by cell-free translation of synthetic mRNAs suggests that the A3 protein has properties similar to A2 (alpha+).

Animals

Evidence that obesity does not influence the vitamin D-endocrine system in blacks.

As compared to nonobese white men and women, age-matched nonobese black subjects and obese white individuals show alterations in the vitamin D-endocrine system that are characterized by increases in mean serum immunoreactive parathyroid hormone (PTH), serum 1,25-dihydroxyvitamin D [1,25-(OH)2D], and urinary cyclic adenosine 3,5-monophosphate (cAMP) and by decreases in mean serum 25-hydroxyvitamin D (25 OHD) and in urinary calcium. Thus, both groups show secondary hyperparathyroidism which is associated with increased renal tubular reabsorption of calcium and increased renal synthesis of 1,25-(OH)2D. In view of these findings, studies were conducted in 10 obese black subjects (3 men and 7 women) and in 12 nonobese black individuals (7 men and 5 women), ranging in age from 20 to 35 yr, to determine whether obesity influences the vitamin D-endocrine system in blacks. Body weight averaged 99 +/- 4 kg in the obese and 73 +/- 3 kg in the nonobese subjects (p less than .001). All of them were hospitalized on a metabolic ward and were given a constant daily diet containing 400 mg of calcium, 900 mg of phosphorus, 110 meq of sodium, 65 meq of potassium, and 18 meq of magnesium.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Measurement of cardiopulmonary function in ventilated neonates with respiratory distress syndrome using rebreathing methodology.

The feasibility of using a multiple gas rebreathing technique to evaluate cardiopulmonary function in the ventilated neonate was assessed by measuring functional residual capacity, diffusing capacity of lung for carbon monoxide, and effective pulmonary capillary blood flow in 10 neonates with respiratory distress syndrome. Measurements were first made on the level of positive end expiratory pressure (PEEP) selected by the clinicians caring for the infants ("clinical" PEEP, mean of 4.4 +/- 0.3 cm H2O). To evaluate the effect of PEEP on cardiopulmonary function, PEEP was then changed above (mean of 6.7 +/- 0.4 cm H2O) and below (mean of 1.9 +/- 0.3 cm H2O) this level and measurements were repeated. Mean functional residual capacity on clinical PEEP (10.8 +/- 1.6 ml/kg) was far below the predicted normal and varied directly with changes in PEEP (mean change of 1.2 ml/kg/cm H2O). Diffusing capacity of the lung for carbon monoxide on clinical PEEP was 0.04 +/- 0.01 ml/min/mm Hg/kg and did not change significantly with changes in PEEP. Mean effective pulmonary capillary blood flow was highest (70 ml/min/kg) at the lowest level of PEEP. However, the effect of increasing PEEP on effective pulmonary capillary blood flow in individual infants varied. Increasing PEEP increased arterial oxygen tension but did not cause changes in systemic arterial pressure or heart rate. We conclude that infants with respiratory distress syndrome have severe lung injury with decreased functional residual capacity and diffusing capacity of the lung for carbon monoxide, and that lung volume improves with the use of PEEP.(ABSTRACT TRUNCATED AT 250 WORDS)

Carbon Monoxide

Evidence for alteration of the vitamin D-endocrine system in obese subjects.

Serum immunoreactive parathyroid hormone (PTH) is increased in obese as compared with nonobese subjects and declines with weight loss. To determine whether alteration of the vitamin D-endocrine system occurs in obesity and whether ensuing secondary hyperparathyroidism is associated with a reduction in urinary calcium, a study was performed in 12 obese white individuals, five men and seven women, and 14 nonobese white subjects, eight men and six women, ranging in age from 20 to 35 yr. Body weight averaged 106 +/- 6 kg in the obese and 68 +/- 2 kg in the nonobese subjects (P less than 0.01). Each of them were hospitalized on a metabolic ward and were given a constant daily diet containing 400 mg of calcium and 900 mg of phosphorus. Whereas mean serum calcium, serum ionized calcium, and serum phosphorus were the same in the two groups, mean serum immunoreactive PTH (518 +/- 48 vs. 243 +/- 33 pg/ml, P less than 0.001), mean serum 1,25-dihydroxyvitamin D [1,25(OH)2D] (37 +/- 2 vs. 29 +/- 2, P less than 0.01), and mean serum Gla protein (33 +/- 2 vs. 24 +/- 2 ng/ml, P less than 0.02) were significantly higher, and mean serum 25-hydroxyvitamin D (25-OHD) (8 +/- 1 vs. 20 +/- 2 ng/ml, P less than 0.001) was significantly lower in the obese than in the nonobese men and women. Mean urinary phosphorus was the same in the two groups, whereas mean urinary calcium (115 +/- 10 vs. 166 +/- 13 mg/d, P less than 0.01) was significantly lower, and mean urinary cyclic AMP (3.18 +/- 0.43 vs. 1.84 +/- 0.25 nM/dl GF, P less than 0.01) and creatinine clearance (216 +/- 13 vs. 173 +/- 6 liter/d, P less than 0.01) were significantly higher in the obese than in the nonobese individuals. There was a significant positive correlation between percentage of ideal body weight and urinary cyclic AMP (r = 0.524, P less than 0.01) and between percentage of ideal body weight and serum immunoreactive PTH (r = 0.717, P less than 0.01) in the two groups. The results provide evidence that alteration of the vitamin D-endocrine system in obese subjects is characterized by secondary hyperparathyroidism which is associated with enhanced renal tubular reabsorption of calcium and increased circulating 1,25(OH)2D. The reduction of serum 25-OHD in them is attributed to feedback inhibition of hepatic synthesis of the precursor by the increased serum 1,25(OH)2D.

Adult

Evidence for alteration of the vitamin D-endocrine system in blacks.

As compared with values in white subjects, bone mass is known to be increased and urinary calcium to be diminished in black individuals. To evaluate the possibility that these changes are associated with alterations in the vitamin D-endocrine system, an investigation was performed in 12 black subjects, 7 men and 5 women, and 14 white subjects, 8 men and 6 women, ranging in age from 20 to 35 yr. All of them were hospitalized on a metabolic ward and were given a constant daily diet containing 400 mg of calcium, 900 mg of phosphorus, and 110 meq of sodium. Whereas mean serum calcium, ionized calcium, and phosphate were the same in the two groups, mean serum immunoreactive parathyroid hormone (350 +/- 34 vs. 225 +/- 26 pg/ml, P less than 0.01) and mean serum 1,25-dihydroxyvitamin D (1,25(OH)2D) (41 +/- 3 vs. 29 +/- 2 pg/ml, P less than 0.01) were significantly higher, and mean serum 25-hydroxy-vitamin D (25-OHD) was significantly lower in the blacks than in the whites (6 +/- 1 vs. 20 +/- 2 ng/ml, P less than 0.001). Mean urinary sodium and 24-h creatinine clearance were the same in the two groups, whereas mean urinary calcium was significantly lower (101 +/- 14 vs. 166 +/- 13 mg/d, P less than 0.01) and mean urinary cyclic AMP was significantly higher (3.11 +/- 0.47 vs. 1.84 +/- 0.25 nM/dl glomerular filtrate, P less than 0.01) in the blacks. Further, the blacks excreted an intravenous calcium load, 15 mg/kg body weight, as efficiently as the whites (49 +/- 3 vs. 53 +/- 3%, NS). Mean serum Gla protein was lower in blacks than in whites (14 +/- 2 vs. 24 +/- 3 ng/ml, P less than 0.02), and increased significantly in both groups in response to 1,25(OH)2D3, 4 micrograms/d for 4 d. There was a blunted response of urinary calcium to 1,25(OH)2D3 in the blacks, and mean serum calcium did not change. The results indicate that alteration of the vitamin D-endocrine system with enhanced renal tubular reabsorption of calcium and increased circulating 1,25(OH)2D as a result of secondary hyperparathyroidism may contribute to the increased bone mass in blacks. Their low serum 25-OHD is attributed to diminished synthesis of vitamin D in the skin because of increased pigment.

Adult

Effects of human erythrocyte guanine nucleotide-binding regulatory protein on parathyroid hormone-responsive adenylate cyclase from canine renal cortex.

We studied the effects of the guanine nucleotide-binding regulatory protein (Gs) from human erythrocytes on PTH-responsive adenylate cyclase from partially purified membranes of canine renal cortex (CRC). Extracts of erythrocyte membranes, containing soluble Gs, was obtained by treatment with a detergent (Lubrol PX). Gs did not stimulate adenylate cyclase activity by itself, but amplified the response of adenylate cyclase in CRC membranes to both synthetic bovine PTH-(1-34) [bPTH-(1-34)] and to the hydrolysis-resistant GTP analog 5'-guanylimido-diphosphate [Gpp(NH)p]. Gs increased PTH stimulation of adenylate cyclase activity in both the presence and absence of Gpp(NH)p. In the absence of Gpp(NH)p, the potentiating effect of Gs occurred only when the concentration of bPTH-(1-34) was greater than 10 ng/ml. bPTH-(1-34), Gpp(NH)p, and Gs each enhanced the catalytic activity of adenylate cyclase when added separately or in combination by increasing the apparent maximum velocity (Vmax) of the enzyme without altering the apparent Km for MgATP. The effect of Gs on CRC membrane adenylate cyclase activity in the presence of NaF (10 mM) and forskolin (100 microM) was also examined. NaF- and forskolin-stimulated enzyme activities were significantly increased by Gs in both the presence and absence of Gpp(NH)p (100 microM). Analysis of double reciprocal plots of substrate concentration and enzyme activity revealed that NaF and forskolin increased the Vmax of the catalytic activity and did not alter the apparent Km of the enzyme for MgATP. These data support the role of Gs as a regulator of the response of adenylate cyclase to hormones, guanyl nucleotides, NaF, and forskolin. Our studies address the relative functional stoichiometry between Gs and catalytic unit present in CRC membranes and suggest that the CRC adenylate cyclase system must contain insufficient Gs to couple with all available catalytic units. These results are consistent with the possibility that deficiency of Gs impairs hormonal stimulation by diminishing the apparent Vmax of the catalytic unit and does not alter the apparent affinity of the enzyme for MgATP.

Adenylyl Cyclases

Evidence for extrarenal production of 1 alpha ,25-dihydroxyvitamin D in man.

Recent studies provide evidence for extrarenal production of 1 alpha ,25-dihydroxyvitamin D [1 alpha ,25(OH)2D]. To investigate this possibility, serum vitamin D, 25-hydroxyvitamin D (25-OHD), 24,25-dihydroxyvitamin D [24,25(OH)2D], and 1 alpha ,25(OH)2D were measured in eight adult anephric subjects. All were undergoing hemodialysis and three of them were receiving vitamin D, 50,000 or 100,000 U/d. Serum vitamin D was elevated in two of the patients given vitamin D and was abnormally low in the others. Mean serum 25-OHD was increased in patients given vitamin D (94.0 +/- 7.6 ng/ml) and was normal in the others (16.4 +/- 0.9 ng/ml, P less than 0.001). Mean serum 24,25(OH)2D was normal in patients given vitamin D (1.38 +/- 0.27 ng/ml) and was low in the others (0.25 +/- 0.08 ng/ml, P less than 0.001). Serum 24,25(OH)2D correlated significantly with serum 25-OHD (r = 0.848, P less than 0.01). Mean serum 1 alpha ,25(OH)2D determined by receptor assay was 5.8 +/- 1.9 pg/ml in patients who were not given vitamin D and was 14.1 +/- 0.6 in those who were given vitamin D (P less than 0.001). Serum 1 alpha ,25(OH)2D correlated significantly with serum 25-OHD (r = 0.911, P less than 0.01). Mean serum 1 alpha ,25(OH)2D, measured by bioassay, was 8.3 +/- 1.9 pg/ml in patients who were given vitamin D and was 15.9 +/- 2.4 pg/ml in those who were given vitamin D (P less than 0.05). There was a significant correlation between the values for serum 1 alpha ,25(OH)2D obtained with the two methods (r = 0.728, P less than 0.01). The results (a) provide evidence in man for extrarenal production of both 24,25(OH)2D and, by two independent assays, of 1 alpha , 25(OH)2D, and (b) indicate that serum values of the two dihydroxy metabolites of vitamin D in anephric subjects vary with the serum concentration of the precursor 25-OHD.

Adult

Clinical characteristics, DNA repair, and complementation groups in xeroderma pigmentosum patients from Egypt.

Xeroderma pigmentosum (XP) has been reported to be unusually frequent among Middle Eastern populations. This report describes the first survey of DNA repair characteristics among Egyptians. Sixteen XP patients were contacted, and biopsies from eight were analyzed for unscheduled DNA synthesis, strand breakage during pyrimidine dimer excision, and complementation groups. The patients were equally distributed between Complementation Groups A and C. Unscheduled synthesis and strand breaks were significantly higher in Group C than in Group A cells. Central nervous system disorders were found in all of the Group A patients and in none of the Group C patients. No clinical symptoms were observed in the heterozygotes. A 2-month-old sib of an XP patient was free of symptoms, but unscheduled synthesis and strand breakage in cultures from this sib were the same as in the related XP homozygote. From the relative frequencies of each complementation group found in various parts of the world, we offer a hypothesis concerning the relative sizes and roles for gene products specified by the alleles or genes corresponding to each complementation group.

Adolescent