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Biomedical subjects

R David

Publications and source records attributed to R David.

At least 181 records · Page 10Linked to original sources

Autologous bone marrow transplantation in the treatment of poor prognosis non-Hodgkin's lymphomas.

Twelve patients with non-Hodgkin's lymphomas of poor prognosis were treated by TACC high-dose chemotherapy (cyclophosphamide 45 mg/kg/day X 4, cytosine arabinoside 200 mg/m2 i.v. q 12 hr X 7,6-thioguanin 100 mg/m2 p.o. X 7 and CCNU 200 or 250 mg/m2 p.o., single dose) followed by autologous bone marrow transplantation (ABMI) (infused dose: 853-20,000 CFU-c/kg). Patients were divided into 2 groups: those in primary therapy with high tumor load (group 1; 3 initial diagnoses, 3 relapses) and those in consolidation therapy for a low tumor load (group 2; 5 complete and 1 partial remissions). Results show that: (1) the aplasia following autologous bone marrow transplantation was short. Leukocyte (greater than 10(9)/1) and platelet (greater than 50 X 10(9)/1) recoveries were observed on day 12 (range, 9-19) and day 14 (range, 8-27). (2) In group 1 there were 3 complete remissions (8,21, 45+ months) and 3 failures, including 1 death to toxicity of TACC. The 3 remissions occurred in patients in primary therapy and overall survival of these patients from the time of initial diagnosis was 48+, 48+ and 60+ months. In group 2 there were 5 persisting complete remissions (12+ to 40+ months) and 1 failure. Overall survival of these patients was 23+, 24+, 27+, 42+ and 70+ months. In both groups failures were associated with contamination of the frozen marrow by tumor. The toxicity of the association TACC + ABMT was acceptable and dominated by the risk of pericardial effusion and infection. The latter was absent in group 2 and occurred in 5/6 cases in group 1. These preliminary results indicate that autologous bone marrow transplantation has a possible role in the aggressive treatment of non-Hodgkin's lymphomas of high-grade malignancy and that its use should preferentially be in the consolidation mode.

Antineoplastic Combined Chemotherapy Protocols↗

A diagnostic approach to suspected obstructive sleep apnea in children.

Most children with obstructive sleep apnea will benefit from tonsillectomy and adenoidectomy. Although polygraphic monitoring remains the definitive diagnostic technique, we wondered if all children suspected of having OSA require such evaluation. We therefore administered a standardized questionnaire to the parents of 23 children with polygraphically proved OSA related to adenotonsillar hypertrophy, 46 age- and sex-matched normal children, and 23 children subsequently referred because of possible OSA. Significantly increased frequencies of the following symptoms were found in the OSA group compared with the control group: difficulty breathing during sleep, 96% vs 2%; apnea observed by the parents, 78% vs 5%; snoring, 96% vs 9%; restless sleep, 78% vs 23%; chronic rhinorrhea, 61% vs 11%; and mouth breathing when awake, 87% vs 18%. Using discriminant analysis, an OSA score was derived that correctly classified all control subjects and 22 of 23 patients with OSA. Considering the data from all groups, we found that (1) OSA scores greater than 3.5 were highly predictive of OSA requiring adenotonsillectomy; (2) no child with an OSA score less than -1 had OSA; and (3) in children with OSA scores between -1 and 3.5, polygraphic monitoring was required to determine the severity of sleep-related airway obstruction and the need for surgical treatment. Use of the OSA score should decrease the need for polygraphic monitoring and facilitate selection of children for tonsillectomy and adenoidectomy.

Adenoids↗

Abnormalities of thyroid function in infants with Down syndrome.

We describe 12 of 1130 infants with Down syndrome in whom various degrees of thyroid dysfunction were detected by neonatal screening. These aberrations were confirmed subsequently in 11 patients. In eight of 11 children, persistent primary hypothyroidism, was diagnosed, whereas in the remaining three patients transient thyroid abnormalities were noted. The twelfth patient died and could not be retested. We found an incidence of persistent primary congenital hypothyroidism in infants with Down syndrome of 1:141, or about 28 times more than in the general population. The cause of thyroid aberrations in these infants remains unclear; none of the studied patients had agenesis or ectopia of the thyroid gland. On initial screening most infants with Down syndrome had only mild biochemical abnormalities, with gradual decompensation occurring thereafter. Infants with Down syndrome are therefore at high risk for congenital hypothyroidism and should have careful follow-up to prevent further deterioration of their mental development or growth.

Child, Preschool↗

Estimated prevalence of glaucomatous blindness in the Negev region of Israel.

An estimate of the prevalence of glaucomatous blindness in the Negev region of Israel was obtained by pooling two sources of available data: a state-run regional registry of blind people and the records of the glaucoma clinic of the Soroka Medical Centre, Beer Sheva. The denominator was the total population insured with the Kupat Holim (Sick Fund) of the Histadrut (General Federation of Labour). Glaucoma was the cause of blindness in only 10% of registered cases. Ninety-five individuals fulfilling the blindness criteria (3/60 or less, or a reduction of the visual field to 20 degrees or less in the better eye) were identified from both sources: this represents a total population prevalence of 39 per 100 000 population and 153 per 100 000 for those aged 41 and over. Glaucomatous blindness was more frequent in males than females, but the risk appeared to increase exponentially with age in both sexes. These data provide a previously lacking quantitative estimate of the prevalence of glaucomatous blindness in the Negev region.

Adult↗

A syndrome of gonadotropin resistance possibly due to a luteinizing hormone receptor defect.

An 18-yr-old 46,XY man with primary hypogonadism and a microphallus is described whose Leydig cells appear to be partially insensitive to gonadotropin action. The external genitalia were well differentiated though abnormally small. The mean +/- SE baseline plasma testosterone (T) level was 62 +/- 3.9 ng/dl, and androstenedione was 34.5 +/- 7.3 ng/dl. Plasma levels of dehydroepiandrosterone, dehydroepiandrosterone sulfate, 17-hydroxyprogesterone, 17-hydroxypregnenolone, corticosterone, deoxycorticosterone, and 17 beta-estradiol were all normal. After the im administration of hCG, plasma T increased insignificantly from 71 to 78 ng/dl, and androstenedione increased from 22 to 47 ng/dl; there was no significant change in the levels of precursor steroids. The mean +/- SE serum FSH level was 17.4 +/- 3.6 mIU/ml, and LH was 15.4 +/- 1.1 mIU/ml (normal, 5-20); both responded briskly to iv GnRH. Exogenous T therapy resulted in normal virilization, whereas therapy with hCG was ineffectual. Testicular biopsy revealed Leydig cells in normal numbers, some spermatogenesis, and thickened tubular basement membranes. In vitro binding studies using [125I]hCG were performed with testicular homogenates from the patient and three normal subjects. With 7.4 fmol labeled hCG, the specific binding (mean +/- SD), expressed as femtomoles of hCG per mg protein, was 1.16 +/- 0.44 compared to 2.49 +/- 0.41 in normal subjects (P less than 0.05). These data demonstrate partial resistance to hCG and suggest that the defect in Leydig cell function may be at the LH receptor or postreceptor level.

Adolescent↗

Biochemical and morphological investigations of the toxicity of a Capmul preparation and a bile salt-EDTA solution in patients with bile duct stones.

Seventeen patients with bile duct calculi were treated alternately with a preparation of glycerol octanoate and a bile salt-EDTA solution via a nasobiliary tube. Of 14 patients (group I), it was necessary to operate on four immediately after irrigation therapy, success resulted from this conservative therapy in eight (57%) cases and two were unchanged. Laboratory investigations showed a decrease in zinc and copper concentrations in the serum. Of the patients 50-60% suffered from vomiting and diarrhea. For three patients (group II), there was an interval of 6-26 days between the end of the therapy and operation. Histological findings in the patients in group I and II subjected to operation included acute ulcerative and chronic inflammation in gallbladder and common bile duct walls. Since the alterations were of minor degree in four of the seven patients who subsequently underwent surgery the risk of irrigation therapy seems to be acceptable.

Aged↗

[Non-Hodgkin's malignant lymphoma. Therapeutic value of autologous bone marrow transplantation].

Twelve patients with non-Hodgkin malignant lymphoma of poor prognosis were treated with heavy chemotherapy of the TACC type (cyclophosphamide 45 mg/kg/day i.v. X 4; cytosine arabinoside 200 mg/m2/12 hours i.v. X 7; 6-thioguanidine 100 mg/m2/12-hourly p.o X 7 and CCNU 200 or 250 mg/m2 p.o. single dose) followed by autologus bone marrow transplantation (853 to 20.000 CFUc/kg). The patients were divided into 2 groups depending on whether they received an induction treatment for large visible tumoral mass (group I: 3 initial presentations, 3 relapses) or a consolidation treatment for small residual tumour (group II: 6 complete and 1 partial remissions). The results show that autologous bone marrow transplantation shortens the duration of the therapeutic aplasia. White cell (greater than 10(9)/l) and platelet (greater than 50.10(9)/l) recovery was observed on days 12 (range 9-19) and 14 (range 8-27) respectively. In group I, 1 patient died of myocardial TACC toxity and acute renal failure on tumoral kidney; there were 2 failures and 3 complete remissions (8, 21, 45 + months). Remissions occurred in patients treated initially; the overall survival since diagnosis was 48+, 48+ and 60+ months. In group II patients there were 1 failure and 5 complete remissions persisting after a 2+ months to 30+ months follow-up; the overall survival was 23+, 24+, 27+, 42+ and 70+ months. The 3 failures in the series occurred in circumstances suggesting contamination of the cryopreserved bone marrow by tumoral cells. The toxicity, largely due to infection, of the TACC-bone marrow transplantation combination was tolerable. It was clearly lower in group II (6 patients, no septicaemia) than in group I (5/6 patients with septicaemia). These preliminary results confirm that there is room for autologous bone marrow transplantation in highly malignant non-Hodgkin lymphomas, particularly during complete remissions to facilitate the use of an aggressive consolidation chemotherapy.

Adult↗

Outcome in neonates with convulsions treated in an intensive care unit.

Neurological and developmental outcome was assessed in 131 survivors of neonatal seizures aged 1 to 5 years who had been treated in a single intensive care unit from 1976 to 1979. Half the children had been born at less than 37 weeks' gestational age, and 28% at 31 weeks or less. Fifty-one children were normal on examination, 17 had minor abnormalities, 25 had moderate disabilities, 30 had severe disabilities, 6 had died because of profound neurological deficits, and 2 could not be located. Recurrent nonfebrile seizures had developed in 26 children. Most children with motor handicaps or visual loss were intellectually retarded, but 10 of 15 children with bilateral hearing loss were intellectually normal. Of 77 children whose seizures were caused by a hypoxic-ischemic insult, 41 developed moderate or severe disabilities. As determined by multivariate analysis, significant neonatal predictors of poor outcome in this group included seizures with late onset, tonic seizures, and seizures lasting for many days. Although seizure frequency and neonatal mortality associated with seizures were greatest in very premature infants, the outcome in premature infants who survived was not significantly different from that of term infants.

Brain↗

Siliceous deposits in human urinary calculi--an E. M. study.

Silica calculi in man are extremely rare; only 12 cases have been reported. In an electron microscopic study of human urinary stones, siliceous deposits were encountered in three out of 180 stones as a discrete component of stones. There were no histories of magnesium trisilicate administration in these cases. Morphology of the deposits was distinctive from any other components of the stones and bore some resemblance to animal silica calculi. Siliceous deposits in human urinary stones appear to be more common than generally recognized.

Electron Probe Microanalysis↗

Delayed kinetics of recovery of haemopoiesis following autologous bone marrow transplantation. The role of excessively rapid marrow freezing rates after the release of fusion heat.

Thirty-five patients were treated by intensive chemotherapy and/or whole-body irradiation followed by reinjection of cryopreserved autologous bone marrow. In 8 patients the kinetics of recovery of haemopoiesis was delayed (recovery to 10(9) leucocytes/litre beyond day 27 and recovery to 50 X 10(9) platelets/litre beyond day 25). This delay was directly responsible for the death of 3 patients and contributed to a fatal outcome in 2 others (mortality rate 9-14%). Retrospective analysis of these 8 cases revealed that failure of autologous transplantation was associated with poor recovery of CFUc, which was in turn related to an excessively rapid freezing rate after the release of fusion heat. Recovery of CFUc to 50% or more was achieved in 100% of cases when the freezing rate was less than 5 degrees C/min, 45% for freezing rates between 5 and 10 degrees C/min and 22% when the freezing rate exceeded 10 degrees C/min (n = 71, P less than 0.001). There was an inverse linear or logarithmic relationship between CFUc recovery and freezing rate after the transition phase (r = -0.46, r = -0.43, P less than 0.001). The quantity of nitrogen introduced into the freezing chamber to annul the fusion heat must therefore be calibrated with accuracy so that the desired shortening of the transition phase will not be accompanied by an overly marked increase in the freezing rate, which would result in the destruction of stem cells. To ensure an adequate freezing rate, it is crucial to monitor the temperature continuously in each sample of bone marrow during the freezing process. This study also suggested that other factors may have interfered with the kinetics of recovery after autologous bone-marrow transplantation. These factors include myelofibrosis, the presence of an Australia antigen and administration of compounds that are toxic for the bone marrow after reinjection of cryopreserved marrow. However, the responsibility of these factors cannot be stated with certainty.

Adult↗

Glaucomatous blindness in the Negev: a descriptive study of age, sex, and ethnic patterns.

Two sources of data (a blind register and the records of a glaucoma clinic) were used to study the age, sex, and ethnic characteristics of sufferers of glaucomatous blindness in the Negev region of Israel. Glaucoma was found to be the cause of blindness relatively infrequently (10% of eyes) among the registered blind population. The rate of blindness from glaucoma in the population was 0.38/1000. Glaucomatous blindness affected more males than females and more individuals of Eastern and Western origin. A steep gradient of increasing number of blind with advancing age was found in both sexes and both ethnic groups, but the gradient was steeper in males and females of Eastern origin. These findings are consistent with the pattern expected of a developing country and represent the first descriptive profile of the pattern of personal characteristics of sufferers from glaucomatous blindness in this region. The ethnic pattern resembles what is known about the natural history of glaucoma in pigmented and nonpigmented races.

Adult↗

Dense-core matrical mitochondrial bodies in oncocytic adenoma of the thyroid.

Single and/or multiple, round and homogeneous electron-dense bodies occurred within the mitochondrial matrix of a mitochondrion-rich follicular adenoma of the thyroid. These non-membrane-bound bodies varied greatly in size and often occupied a large portion of the mitochondrion. They were present in normal-sized or large mitochondria that exhibited cristolysis and/or dilatation of the intracristal space of the residual cristae and formation of intramatrical myelin figures. The globule-containing mitochondria frequently exhibited bundles of parallel intramatrical filamentous inclusions that were 6 to 8 nm in width and were randomly arranged in clusters. Megamitochondria up to 4.4 micrometers in widest diameter occurred in a frequency of one to two per cell and they displayed similar bundles of filamentous inclusions. This evidence of electron-dense bodies in non-steroid-hormone-secreting cells suggests that the bodies result from nonspecific mitochondrial reaction to injury rather than being inclusions specific for steroid-synthesizing cells.

Adenoma↗

Fatal barium embolization due to incorrect vaginal rather than colonic insertion. An ultrastructural and x-ray microanalysis study.

Fatal generalized barium sulfate (BaSO4) embolization followed erroneous vaginal insertion of the enema tip intended for colon examination. Light microscopy revealed the presence of swollen, granular reticuloendothelial cells in most visceral organs such as lung, liver, spleen, bone marrow, kidney, and brain. Transmission electron microscopy showed the reticuloendothelial cells loaded with uniformly electron-dense granules of various sizes. Scanning electron microscopy equipped with an energy-dispersive x-ray analyzer confirmed the BaSO4 composition of these granules when unstained paraffin sections of different organs mounted on glass slides without coverslips were examined. The use of the technique of x-ray microanalysis is recommended when absolute identification of inorganic material in human organs is needed. The technique can be used directly on routine paraffin-embedded material mounted on glass slides as well as with material expressly prepared.

Age Factors↗

Extrahepatic biliary obstruction and liver failure secondary to myeloma of the pancreas.

An unusual case of multiple myeloma in an 88-year-old patient is described. Besides skeletal involvement, there was myeloma of the thoracic and abdominal lymph nodes and of the liver and pancreas. In the pancreas, the myeloma extensively involved the head and body, and on computerized tomography scan was suggestive of a pancreatic carcinoma. The myeloma caused extrinsic compression of the common bile duct, resulting in severe jaundice and hepatic and renal failure. To the author's knowledge this is the second such case of pancreatic myeloma causing extrahepatic biliary obstruction.

Acute Kidney Injury↗

beta-Fibrillary bodies in low-grade adenocarcinoma of parotid gland: a histochemical and ultrastructural study.

Rounded or polyhedral, acellular, dense lamellated structures were seen within the cystic and glandular spaces in a case of low-grade papillary adenocarcinoma of the parotid gland. These structures displayed the histochemical characteristics of amyloid, namely, pink color with apple-green birefringence and bright red fluorescence with alkaline congo red, orthochromasia and red birefringence with standardized toluidine blue, positive dimethylaminobenzaldehyde nitrite and diazotization coupling reactions, and spontaneous autofluorescence. At the ultrastructural level the tumor consisted of cuboid, flattened, or elongated epithelial cells with varying degrees of differentiation, but most mature tumor cells had numerous intracellular intermediate filaments. These filaments were randomly oriented and had no lateral fasciation; they were 10 nm wide and similar to those constituting the intraluminal corpora amylacea. These bodies displayed increased fibrillary density. Cellular organelles and pyknotic nuclei were frequently present at the periphery of the fibrillary masses. Amyloid masses, histochemically and ultrastructurally indistinguishable from those in the lumens, were present in the stroma as well. It is postulated that both stromal and intraluminal beta-fibrillary bodies result from apoptosis and desquamation of neoplastic cells, with progressive release and confluency of intracellular intermediate filaments within closed cystic spaces. This additional evidence of beta-fibrillosis associated with a slow-growing non-hormone-secreting salivary gland tumor suggests that these tumors may be associated with amyloidosis more frequently than was previously suspected.

Adenocarcinoma, Papillary↗