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Biomedical subjects

M Weiner

Publications and source records attributed to M Weiner.

At least 145 records · Page 8Linked to original sources

Promotion of family enrollment in an urban family practice residency program.

Although a basic goal of family practice is to provide care for all members of the family, few studies have been done to test the ease of accomplishing this goal. At the Downstate Medical Center Department of Family Practice in Brooklyn, New York, an attempt was made to increase family enrollment by introducing several educational interventions directed at patients and resident physicians. Family enrollment levels were documented during a study period from June 1981 to September 1982, and again in June 1984. Both before and after the intervention efforts, family enrollment levels remained the same. It was concluded that the educational interventions used were unsuccessful in both short-term and long-term follow-up. Only one subgroup that participated in a specific educational intervention (patient orientation groups) showed an increase in family enrollment.

Family↗

Age-related increased susceptibility of male Fischer 344 rats to acetaminophen nephrotoxicity.

Male Fischer 344 rats classified as young (2-4 months), middle-aged (12-14 months) and aged (22-25 months) received 300, 600 or 800 mg/kg acetaminophen (APAP) intraperitoneally and were sacrificed 24 hr later. Blood urea nitrogen (BUN) concentration and urinary glucose and osmolality were determined. In addition, kidneys were evaluated for histopathological changes. APAP did not affect osmolality or BUN concentrations and failed to produce lesions after any dose in young rats. Osmolality was decreased 40% and 50% in middle-aged and aged rats, respectively, after 800 mg/kg APAP. Glucosuria was prominent in aged rats after the 600 and 800 mg/kg doses were administered, while middle-aged rats showed little glucosuria after these doses. BUN concentrations were elevated 89% and 183% in middle-aged and aged rats, respectively, given 600 mg/kg APAP; after 800 mg/kg, BUN concentrations were elevated approximately four-fold in both age groups. Pathological evaluations showed a greater incidence of acute tubular necrosis (ATN) in aged kidneys compared to kidneys of middle-aged rats after 600 mg/kg, while the two older groups exhibited similar, more severe ATN after 800 mg/kg APAP. These data suggest an age-related increased susceptibility of male Fisher 344 rats to APAP nephrotoxicity.

Acetaminophen↗

Ocular involvement in congenital leukemia.

Congenital leukemia, a rare disease with distinct features, was diagnosed in a 5-week-old girl. The infant was tachypneic and tachycardic, with intercostal retractions, distended abdomen, and multiple hematomas. Despite aggressive treatment, the child died. Histologic examination of tissue obtained at autopsy disclosed leukemic infiltrates in the ocular muscles, conjunctiva, uveal tract, and optic nerve.

Anterior Eye Segment↗

Effect of inositol hexaphosphate on the transient behavior of red cells following a DMSO-induced osmotic pulse.

An osmotic pulse can be used to incorporate inositol hexaphosphate (IHP) into red cells. The pulse is induced by equilibrating a red cell suspension with DMSO and then rapidly diluting with an isotonic IHP solution. Since IHP binds to hemoglobin and lowers the affinity for oxygen, this method may find application in the preparation of low-affinity cells for experimental and clinical use. The experiments reported here examined the dynamic changes of several red cell variables immediately following the osmotic pulse. The effect of IHP, which has been shown to dissociate red cell cytoskeletons, was evaluated by comparison with a matched phosphate-buffered saline (PBS) diluent. Red cell morphology, volume, and hemoglobin permeability were studied by fixing the cells at times ranging from 0.06 to 300 sec after dilution. Mechanical fragility was measured by subjecting the cells to a short period of shear stress at the same times after dilution. With both diluents, the cells underwent a rapid increase in volume followed by a return towards normal volume with a maximum at less than 250 msec. With IHP diluent, the period of hemoglobin permeability immediately followed the size peak and was completed by about 1 sec after dilution. PBS also induced a second leakage at longer times (10-120 sec), which resulted in a morphological dichotomy with ghosts and intact cells. The choice of diluent also affected sensitivity to shear stress. The IHP-treated cells had a mechanical fragility maximum at about 1 sec. The PBS-treated cells exhibited no enhanced mechanical fragility. An unexpected result was the inhibition of the second phase of lysis in PBS-treated cells by a properly timed shear stress.

Cell Membrane Permeability↗

The development of acetaminophen-induced nephrotoxicity in male Fischer 344 rats of different ages.

Male Fischer 344 rats classified as young (2-4 months), middle-aged (12-15 months) and aged (22-25 months) were administered 600 mg/kg acetaminophen (APAP) IP. Rats were killed 6 and 12 h after dosing, and renal damage evaluated by blood urea nitrogen (BUN) levels and histopathology. In addition, plasma levels of APAP and its sulfate and glucuronide conjugates were determined after 6 h. There was no evidence of renal damage in any age group 6 h after APAP. While no nephrotoxicity was present in young animals after 12 h, BUN was elevated 94% and 214% in middle-aged and aged rats, respectively, compared to young animals. At 12 h, APAP-induced renal lesions were more severe in aged rats compared to middle-aged animals. APAP-induced renal damage, as judged by BUN and histopathology, was not altered in young or middle-aged rats following unilateral nephrectomy. Six hours after APAP, both the middle-aged and aged animals had significantly higher plasma levels of APAP and APAP glucuronide compared to young rats. There were similar amounts of the sulfate conjugate in the plasma of each age group. This suggests pharmacokinetic differences could contribute to the age-related increased susceptibility of male Fischer 344 rats to APAP-induced nephrotoxicity.

Acetaminophen↗

Reversible respiratory muscle weakness in hypothyroidism.

Physiological studies performed 1 week after initiation of thyroid replacement showed persistence of significant respiratory muscle weakness in a patient presenting with hypothyroidism and hypercapnia. Repeat studies 12 months later demonstrated return of respiratory muscle strength to normal. Earlier reports on respiratory failure in hypothyroidism had postulated a critical role for respiratory muscle weakness in the genesis of hypercapnia. Since hypercapnia was rapidly reversed despite the persistence of severe respiratory muscle weakness, this explanation may not be always correct. It appears than in our patient thyroid replacement had its primary effect on the respiratory control system.

Aged↗

Activation of liver tryptophan oxygenase by hydrocortisone, hematin and tryptophan in streptozotocin-diabetic rats.

This study compared changes in liver tryptophan oxygenase (TPO) activity in response to hydrocortisone, hematin and tryptophan administration to non-diabetic and diabetic (streptozotocin) rats. Hydrocortisone caused similar increases in apoenzyme (inactive), holoenzyme (heme-saturated) and total (holoenzyme + apoenzyme) TPO activities in non-diabetic and diabetic rats. The ability of hematin to increase total TPO activity was significantly less in diabetic rats. The largest differences between diabetic and non-diabetic rats were found with tryptophan which increased total TPO and holoenzyme activities 300% and 650% respectively in non-diabetic rats. However, tryptophan increased both apoenzyme (unchanged in non-diabetic rats) and holoenzyme activities by 300% in diabetic rats. These results indicate that in the diabetic state, the TPO-heme conjugation process is impaired, especially substrate mediated TPO-heme saturation.

Animals↗

Preparation of low-affinity red cells with dimethylsulfoxide-mediated inositol hexaphosphate incorporation: hemoglobin and ATP recovery using a continuous-flow method.

Incorporation of IHP into red cells decreases oxygen affinity as a result of the binding of this compound to the 2,3-DPG site of hemoglobin. This investigation describes a continuous-flow method which utilizes the osmotic pulse technique to transport IHP into RBC. Using this procedure, it is possible to obtain a significant increase in P50 while maintaining in vitro cellular integrity. For example, IHP incorporation sufficient to cause an increase in the P50 of 20 mm Hg may be achieved with recovery of approximately 75% of the hemoglobin and with maintenance of ATP levels compatible with good viability. The continuous-flow method allows uniform treatment of large, unit-size volumes of red cells with a relatively small quantity of reagents. The final cell product is macrocytic/hypochromic with an increased number of stomatocytes.

Adenosine Triphosphate↗

Effect of nursing-staff support groups on the quality of newborn intensive care.

ICU support groups are widely recommended to mitigate the effects of stress on staff performance, thereby improving patient care. The usefulness of a nursing-staff support group was assessed in the neonatal ICUs of both a city/county hospital (10,000 births/yr) and a private hospital (3200 births/yr). Support-group meetings focused on communication and patient care and were conducted every 1 to 2 wk by psychiatrists experienced in intensive care support groups. Nevertheless, attendance diminished and the groups lasted only 6 to 7 months. Moreover, the quality of routine, emergency, and overall care did not differ significantly during intervention vs. control months. Our findings suggest that sources of ICU stress may be best addressed by methods other than nursing-staff support groups. Under the conditions of the study, we found little evidence to justify the expense and effort required to conduct ICU support groups.

Crisis Intervention↗

In vitro models reflecting the action of strong acids on integumental tissue.

The discoloration of white rat hair by acid preparations has been employed as a model reflecting local tissue destruction by intravital fixation as contrasted to tissue dissolution. Nitrate reduction products in equilibrium with nitrite ion in moderately strong acid result in much more rapid tissue fixation than is accomplished by acid preparations alone. Parallel differences were found in the color reaction of normal skin to different acid preparations. The rapid fixing capacity demonstrated by these models may be useful for sharply localized destruction of topical lesions clinically.

Animals↗

Double-blind study of variables influencing the clinical effect of Solcoderm.

Double-blind clinical studies of pairs of lesions were initiated to evaluate several components of Solcoderm treatment. The superiority of Solcoderm over plain nitric acid was as evident with plastic as with wooden applicators. A mixture of oxalic and nitric acid had effects similar to Solcoderm, while acetic and nitric acid was similar in effect to plain nitric acid.

Acetates↗

Diabetes-induced metabolic alterations in heme synthesis and degradation and various heme-containing enzymes in female rats.

Diabetes-induced alterations in heme and hemoproteins, as well as its relationship to drug-mediated induction of ALA Synthase (ALA-S), were examined in female Sprague-Dawley rats. Animals were rendered diabetic by a single i.v. injection of streptozotocin (STZ, 65 mg/kg) and measurements were made at various times after treatment. The basal levels of the key enzymes involved in heme synthesis, ALA-S and ALA-dehydratase (ALA-D), were decreased about 36% and 54%, respectively, 44-46 days after diabetes induction. Furthermore, the catabolism of heme that occurs via microsomal heme oxygenase progressively decreases in activity during the course of diabetes, and reaches 69% of control in 90-day diabetic animals. The basal levels of heme, cytochromes P-450 and b5 were elevated about twofold in diabetic rats as compared with their corresponding control values. The activity of benzo(a)pyrene hydroxylase in diabetic rats was also increased in proportion to the microsomal content of cytochrome P-450. In contrast, delta 4-hydrogenase, the rate-limiting enzyme in corticosterone metabolism, exhibited a 35-65% decrease in activity throughout the experimental period. Tryptophan pyrrolase activity (total, holo-, and apoenzyme) was elevated about 2.5-fold in STZ diabetic rats. In vivo insulin therapy of diabetic animals antagonized the effect of the diabetic state on the above measured parameters. Treatment with aminoglutethimide resulted in about a twofold elevation in ALA-S activity in control as well as chronically diabetic rats. However, a similar stimulatory response in ALA-S activity to CoCl2 administration was observed only in control or insulin-treated diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)

5-Aminolevulinate Synthetase↗

Heme and hemoproteins in streptozotocin-diabetic female rats.

Alterations in heme biosynthetic and degradative capabilities and in the activities of several heme-containing enzymes were examined in hepatic tissues of streptozotocin (STZ)-diabetic female Sprague-Dawley rats. Activities were measured 10, 30 and 90 days following the administration of STZ (65 mg/kg, i.v.). The activities of the key enzymes involved in heme synthesis, delta-aminolevulinic acid (ALA) synthase, ALA dehydratase, and uroporphyrinogen synthase, were decreased markedly in STZ-diabetic rats as compared to sham-operated animals. Furthermore, the catabolism of heme which occurs via microsomal heme oxygenase (MHO) remained unaltered in these animals. Microsomal content of heme and cytochrome P-450, and the activities of tryptophan pyrrolase and the drug-metabolizing enzymes benzo[a]pyrene (BP) hydroxylase and aniline hydroxylase, were increased in the livers of diabetic rats. By contrast, the activity of the heme-containing enzyme catalase was decreased in these animals. Cobalt chloride produced a marked increase in MHO with a concomitant decrease in microsomal content of cytochrome P-450 and its associated BP hydroxylase activity in normal as well as chronically diabetic rats. It was of interest, however, that the increase in ALA synthase that is normally produced by this metal was not seen in chronic diabetic animals. Thus, chronic diabetes produced subtle and important disruptions in cellular metabolism, which may have been the result of long-term alterations in key enzymes involved in heme synthesis.

5-Aminolevulinate Synthetase↗

Incorporation of inositol hexaphosphate into red blood cells mediated by dimethyl sulfoxide.

Inositol hexaphosphate (IHP) binds to deoxyhemoglobin and markedly decreases the affinity of hemoglobin for oxygen. We introduce here a method for incorporating this polyphosphate into erythrocytes, thus preparing very low affinity cells for use in respiration research. The method uses dimethyl sulfoxide (DMSO) to facilitate entry of IHP. The cells are exposed to a high concentration of DMSO which is rapidly diluted with IHP solution. During this dilution the cells become leaky and IHP enters. The influence of several variables at each step of the process has been investigated and the data support a transient osmotic gradient mechanism for IHP incorporation.

Dimethyl Sulfoxide↗

Adjuvant chemotherapy of malignant fibrous histiocytoma of bone.

Malignant fibrous histiocytoma (MFH) is a pleomorphic sarcoma that is uncommon in children. It most frequently arises from the soft tissues; however, it has been recently established that primary bone MFH also exists. Surgical resection or amputation is the cornerstone of treatment for MFH of bone. But, with this modality of therapy alone the majority of patients develop either distant metastases or local recurrence. This study reports on three adolescent girls with MFH of bone who were successfully treated with radical resection and 18 months of adjuvant chemotherapy with vincristine, high dose methotrexate, Citrovorum Factor rescue, and Adriamycin. All three patients remain disease-free for a follow-up period of 42-48 months. The current regimen was well tolerated. Morbidity was minimal, with no patient developing any significant drug-related complications. The adjuvant chemotherapy regimen described appears to be effective in prolonging survival in patients with MFH of bone and appears to warrant further study in additional patients.

Adolescent↗