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Biomedical subjects

R Rothman

Publications and source records attributed to R Rothman.

At least 19 recordsLinked to original sources
PubMed2004

Multilineage hematopoietic engraftment after allogeneic peripheral blood stem cell transplantation without conditioning in SCID patients.

Successful stem cell transplantation for patients with severe combined immunodeficiency (SCID) from matched family donors without conditioning results in engraftment of T lymphocytes. B lymphocytes engraft in only 50% of the cases, while myelopoiesis and erythropoiesis remain of host origin. Full hematopoietic engraftment was reported in one case after bone marrow transplantation without conditioning for a SCID patient. We studied three SCID patients who were transplanted with unmodified mobilized peripheral blood from HLA-identical family sex-mismatched members. They received megadoses of stem cells (18-23 x 10(6)CD34/kg). In contrast to the expected mixed chimerism that usually occurs in the absence of conditioning, we found in our patients 100% donor cell engraftment based on fluorescence in situ hybridization (FISH) and microsatellite techniques. Subset analysis of the engrafted cells using a multiparametric system enabling a combined analysis of morphology, immunophenotyping and FISH showed that both T and B lymphocytes and myeloid cells were of donor origin in two patients, while T lymphocytes and myeloid cells were of donor origin in the third. In the two cases with ABO incompatibility, erythroid engraftment was evidenced by blood group conversion from recipient to donor type. Multilineage donor engraftment is possible in SCID patients even without conditioning.

B-Lymphocytes↗
PubMed1999

Effects of antihistamines on 3, 4-methylenedioxymethamphetamine-induced depletion of serotonin in rats.

This study investigated the effects of chlorpheniramine (CPA, 10-25 mg/kg), diphenhydramine (DIPH, 20 mg/kg), tripelennamine (TRIP, 20 mg/kg), and pyrilamine (PYRI, 20 mg/kg) on 3, 4-methylenedioxymethamphetamine (MDMA, 20 mg/kg x 2)-induced hyperthermia and depletion of indoles in rat brains, on the uptake of serotonin and dopamine into rat synaptosomes, on the binding affinity of CPA for biogenic amine transporters in the synaptosomes of rat brain, and on the scavenging hydroxyl free radicals activity. Rats were treated with two injections of MDMA, CPA, DIPH, TRIP, PYRI, and saline, alone or in combination of MDMA with one of the antihistamines, 6 h apart and sacrificed 5 days later. Rectal temperature was measured prior to and hourly following the drug injections for 13 h. As compared to saline controls, MDMA increased body temperature and decreased levels of indoles, measured by HPLC, in several brain regions of rats. CPA attenuated and DIPH had no effect on MDMA-induced hyperthermia, yet both attenuated the depletion of indoles, whereas PYRI and TRIP potentiated these effects. CPA inhibited the binding of [(3)H]paroxetine and [(3)H]nisoxetine to the synaptosomes of cerebral cortex and of [(3)H]win 35,428 to the synaptosomes of striatum. CPA, DIPH, TRIP, and PYRI inhibited [(3)H]serotonin uptake. CPA, PYRI, and TRIP, but not DIPH, scavenge hydroxyl radicals. Possible mechanisms of the different effects of the antihistamines on MDMA-induced hyperthermia and depletion of serotonin are discussed. Published 1999 Wiley-Liss, Inc.

Adrenergic Uptake Inhibitors↗
PubMed1999

Alcohol and other psychoactive drugs in trauma patients aged 10-14 years.

OBJECTIVE: To examine the prevalence of alcohol and/or other psychoactive drugs, such as marijuana and cocaine (AODs), involved in preteen trauma patients. METHODS: Toxicological testing results were analyzed for 1356 trauma patients aged 10-14 years recorded in the National Pediatric Trauma Registry for the years 1990-95. RESULTS: Of the 1356 patients who received toxicological screening at the time of admission, 116 (9%) were positive for AODs. AOD involvement increased with age. Patients with pre-existing mental disorders were nearly three times as likely as other patients to be AOD positive (23% v 8%, p < 0.01). AOD involvement was more prevalent in intentional injuries and in injuries that occurred at home. CONCLUSIONS: AODs in preteen trauma are of valid concern, in particular among patients with mental disorders or intentional injuries. The role of AODs in childhood injuries needs to be further examined using standard screening instruments and representative study samples.

Adolescent↗
PubMed1999

Dose-related neurobehavioral effects of chronic cocaine use.

Although cocaine use is a significant public health problem, there is a paucity of scientific data on long-term neurobehavioral effects. This study examined the dose-related association between chronic cocaine use and neurobehavioral performance. A battery of neuropsychological tests was administered to 30 abstinent chronic cocaine abusers and 21 non-drug-using control subjects matched for age, education, and intelligence. After controlling for age, education, and intellectual ability, greater use of cocaine (grams per week) was associated with larger decrements on tests measuring executive functioning, visuoperception, psychomotor speed, and manual dexterity. These results suggest that chronic cocaine use is associated with persistent decrements in cognitive function that are most pronounced in heavy users. Knowledge of specific cognitive processing deficits in chronic cocaine users would be useful for designing individually tailored drug treatment programs.

Adult↗
PubMed1998

Epidemiology of alcohol-related emergency department visits.

OBJECTIVE: To examine the population and geographic patterns, patient characteristics, and clinical presentations and outcomes of alcohol-related ED visits at a national level. METHODS: Cross-sectional data on a probability sample of 21,886 ED visits from the 1995 National Hospital Ambulatory Medical Care Survey were analyzed with consideration of the individual patient visit weight. The annual number and rates of alcohol-related ED visits were computed based on weighted analysis in relation to demographic characteristics and geographic region. Specific variables of alcohol-related ED visits examined included demographic and medical characteristics, patient-reported reasons for visit, and physicians' principal diagnoses. RESULTS: Of the 96.5 million ED visits in 1995, an estimated 2.6 million (2.7%) were related to alcohol abuse. The overall annual rate of alcohol-related ED visits was 10.0 visits per 1,000 population [95% confidence interval (CI) 8.7-11.3]. Higher rates were found for men (14.7 per 1,000, 95% CI 12.5-16.9), adults aged 25 to 44 years (17.8 per 1,000, 95% CI 15.0-20.6), blacks (18.1 per 1,000, 95% CI 14.0-22.1), and residents living in the northeast region (15.2 per 1,000, 95% CI 12.1-18.2). Patients whose visits were alcohol-related were more likely than other patients to be uninsured, smokers, or depressive. Alcohol-related ED visits were 1.6 times as likely as other visits to be injury-related, and 1.8 times as likely to be rated as "urgent" or "emergent." The leading principal reasons for alcohol-related ED visits were complaints of pain, injury, and drinking problems. Alcohol abuse/dependence was the principal diagnosis for 20% of the alcohol-related visits. CONCLUSION: Alcohol abuse poses a major burden on the emergency medical care system. The age, gender, and geographic characteristics of alcohol-related ED visits are consistent with drinking patterns in the general population.

Adult↗
PubMed1995

Brain and plasma levels of opioid peptides are altered in rats with thioacetamide-induced fulminant hepatic failure: implications for the treatment of hepatic encephalopathy with opioid antagonists.

Although plasma levels of Met-enkephalin and beta-endorphin are elevated in patients suffering from liver failure, it is not known whether central nervous system (CNS) opioidergic neurotransmission is altered in these patients. Such changes may contribute to the motor dysfunction, psychiatric abnormalities and CNS depression observed in hepatic encephalopathy (HE). Therefore, Met- and Leu-enkephalin, dynorphin A and beta-endorphin levels were measured in discrete brain regions and plasma from thioacetamide-treated rats in Stages II to IV of HE. Pituitary and plasma beta-endorphin, Met- and Leu-enkephalin concentrations increased with the severity of HE by 50 to 290%. Pituitary and brainstem dynorphin A levels increased whereas plasma levels decreased in rats with thioacetamide-induced fulminant hepatic failure. Both striatal Met- and Leu-enkephalin levels increased and hypothalamic concentrations decreased in HE. Concurrent with the increase in striatal Met-enkephalin levels was a 26 to 48% decrease in the density of striatal and hypothalamic delta receptors. No change in either the density or affinity of radioligand binding to mu or delta receptors was observed in the CNS. Finally, administering (+/-)-naloxone (5 and 10 mg/kg) or (+/-)-naltrexone (5-15 mg/kg), but not (+)-naloxone (10 mg/kg), significantly increased the motor activity of rats with Stage III HE. Whereas elevated plasma levels of opioid peptides may play a role in the peripheral manifestations of hepatic failure (ascites and hypotension), increased CNS levels of these peptides may be involved in the neuropsychiatric abnormalities characteristic of HE. Thus, opioid antagonists may be effective in ameliorating some of the neurological manifestations of HE.

Animals↗
PubMed1994

Interleukin 4 receptor signaling in human monocytes and U937 cells involves the activation of a phosphatidylcholine-specific phospholipase C: a comparison with chemotactic peptide, FMLP, phospholipase D, and sphingomyelinase.

Interleukin 4 (IL-4) diminishes cytokine activation of human macrophage. IL-4 binding to monocyte IL-4R is associated with protein kinase C (PKC) translocation to a nuclear fraction. The cleavage of diacyglycerol (DAG), an activator of PKC, from membrane phospholipids was investigated to define the proximal events of IL-4R signaling. IL-4 induced a statistically significant time-and dose-dependent generation of DAG. The IL-4-triggered production of DAG was not derived from phosphatidylinositol 4,5-bisphosphate (PIP2) hydrolysis, since neither cytosolic calcium flux nor liberation of inositol phosphates was detected in response to IL-4. Experiments were performed using [14C-methyl]choline-labeled U937 cells and monocytes to determine whether IL-4R activated phospholipase C (PLC), PLD, or PLA2 to use membrane phosphatidylcholine (PC) to form DAG. IL-4 induced a time- and dose-dependent increase of phosphocholine (pchol) with concomitant degradation of membrane PC (p < 0.05 compared with control). The finding that the peak reduction of PC was equivalent to peak production of pchol suggested that IL-4R signaling involved the activation of a PC-specific PLC. Changes in choline (chol) or lyso-PC and glycerolphosphocholine, the respective products of PC cleavage by PLD or PLA2, were not detected in IL-4-treated cells. In contrast, exogenous PLD induced an increase in chol and concomitant loss of membrane PC. Additional investigation suggested that IL-4R signaling does not involve PLD. In cells labeled with L-lyso-3-PC 1-[1-14C]palmitoyl, PLD but not IL-4, increased the production of phosphatidic acid (PA) and phosphatidyl-ethanol when pretreated with ethanol. Propranolol, an inhibitor of phosphatidate phosphohydrolase, and calyculin A, a phosphatase 1 and 2A inhibitor, blocked DAG production in response to FMLP but not to IL-4. In propranolol pretreated cells, PMA but not IL-4 triggered the production of PA and lowered the amount of DAG. Evidence that PLA2 is not coupled to IL-4R is the detection of arachidonate production in response to FMLP but not to IL-4. Furthermore, IL-4R is not coupled to sphingomyelinase (SMase) since IL-4, unlike exogenous SMase, did not generate ceramide but induced the hydrolysis of PC to pchol that was comparable to exogenous PLC. In summary, IL-4R signaling in monocytes and U937 cells involves PLC and not PLD, PLA2, or SMase, and it uses PC and not PIP2 to form DAG.

Arachidonic Acid↗
PubMed1994

Taperloc femoral component. A 2-6-year study of the first 100 consecutive cases.

The first 100 consecutive patients who underwent insertion of the Taperloc (Biomet, Warsaw, IN) femoral stem were prospectively studied with a mean follow-up period of 3.8 years (range, 2-6 years). Two of the original 100 patients were lost, giving a 98% follow-up rate. The diagnoses included osteoarthritis (76 patients), avascular necrosis (19), rheumatoid arthritis (3), chrondrolysis (1), and post-traumatic arthritis (1). The mean age at surgery was 56 years (range, 25-79 years), mean weight was 78 kg (range, 45-127 kg), and the female to male ratio was 29:71. Charnley pain and function scores were 3.0 and 2.8 before surgery and 5.5 and 5.4 after surgery. Thigh pain was present in 2% of the patients at the final follow-up evaluation. There were no revisions. Radiographic signs of bone-ingrowth fixation (calcar atrophy, spot welds) were seen in 92 of 94 components (98%). No component had complete demarcation of the porous-coated zones. Fifty-two of 94 patients were able to be matched for age, sex, weight, diagnosis, and length of follow-up period with a series of patients who received a contemporary cemented total hip. In this matched subset, the Charnley pain and function scores were 5.6 and 5.5 for the cementless Taperloc stem and 5.7 and 5.5 for the cemented control group; this is not a significant difference. These data indicate a clinical performance equivalent to a matched group of contemporary cemented total hip arthroplasties.

Adult↗
PubMed1994

Attenuation of methamphetamine-induced neurotoxicity in copper/zinc superoxide dismutase transgenic mice.

Administration of methamphetamine (METH) to rats and nonhuman primates causes loss of terminals in the nigrostriatal dopaminergic system. The mechanism by which METH causes its neurotoxicity is not known. To evaluate further the role of oxyradicals in METH-induced neurotoxicity, we have tested its effects in CuZn superoxide dismutase (SOD) transgenic (Tg) mice, which express the human CuZnSOD gene. In non-Tg mice, acute METH administration causes significant decreases in levels of dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) in the striata and cortices of non-Tg mice. In contrast, there were no significant decreases in cortical or striatal DA in the SOD-Tg mice. The effects of METH on DOPAC were also attenuated in both structures of these SOD-Tg mice. Chronic METH administration caused decreases in levels of striatal DA and DOPAC in the non-Tg mice, whereas the SOD-Tg mice were not affected. These results suggest that METH-induced dopaminergic toxicity in mice may be secondary to increased production of reactive oxygen species such as the superoxide radical.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

Exclusion of type II and type VI procollagen gene mutations in a five-generation family with multiple epiphyseal dysplasia.

We have studied a family with an autosomal dominant form of multiple epiphyseal dysplasia (MED) inherited through at least 5 generations. Bilateral deformity of the hips with subsequent degenerative arthritis was the most common and most severe change observed in the affected relatives. Abnormalities of the knees, ankles, and shoulders were also noted in some affected individuals. Radiological examination showed changes in affected joints consistent with epiphyseal dysplasia. In early stages, the articular surfaces appeared flattened or irregular in shape. In advanced stages, epiphyseal fragmentation, joint surface erosion, and extensive remodeling were observed. The abnormalities of the epiphyses suggested that the primary defect might be in a structural component of the epiphyseal cartilage matrix. The gene encoding type II collagen (COL2A1) was tested for genetic linkage to MED in this family by restriction fragment length polymorphism (RFLP) analysis. Recombination between COL2A1 and MED was observed, ruling out COL2A1 as the site of the mutation. The genes encoding the 3 chains of type VI collagen were also excluded on the basis of discordant inheritance. The disease in this family is therefore not the result of mutations in the genes encoding type II or type VI collagen.

Adult↗
PubMed1993

The evaluation and management of known or suspected stones of the common bile duct in the era of minimal access surgery.

Laparoscopic cholecystectomy (LC) has rapidly become the procedure of choice for symptomatic cholelithiasis. The perioperative diagnosis and modern treatment of suspected stones of the common bile duct (CBD) remains controversial. A database of 573 patients undergoing LC was compiled during an 11 month period. Sixty-seven patients (47 females, 20 males) (13 percent) were suspected of having CBD stones based upon clinical, laboratory and roentgenographic evidence. Fifty-two patients underwent endoscopic retrograde cholangiopancreatography (ER-CP) (45 preoperative and seven postoperative). Seventeen patients were studied with intraoperative cholangiogram (IOC). The indications for cholangiography (either ERCP or IOC) included pancreatitis (group 1), clinical history suggestive of CBD stones, but normal preoperative liver function tests (LFT) (group 2), cholangitis (group 3), grossly abnormal LFT (group 4) and dilated CBD (greater than 7 millimeters on sonogram) (group 5). The incidence of CBD stones was three of 14 (21 percent) in group 1, six of 20 (30 percent) in group 2, two of three (67 percent) in group 3, 16 of 26 (62 percent) in group 4 and two of four (50 percent) in group 5. Overall, 29 patients (23 females and six males) had stones retrieved from the CBD. Of the 52 ERCP, 20 endoscopic sphincterotomies were performed for documented CBD stones. Of the group that had pre-LC ERCP, three (6 percent) ultimately required an open procedure. There were three instances of post-ERCP pancreatitis (6 percent) and ERCP was not able to opacify or clear the CBD in four instances. Seven patients had postoperative ERCP with successful retrieval of retained CBD stones (100 percent). Of the 17 IOC, eight were positive--two patients underwent laparoscopic clearance of the CBD and six required conversion to an open procedure. There were no deaths or extensive complications. Total and direct bilirubin, alkaline phosphatase and serum glutamic pyruvic transaminase were independently related to the presence of a CBD stone, while demographic data, past medical history, preoperative symptoms, leukocyte count, vital signs, amylase, serum glutamic-oxalacetic transaminase nuclear scintigraphic visualization of the duodenum or size of CBD on sonography, were not. No patient with biliary pancreatitis had CBD stones without abnormalities in the LFT or the preoperative sonogram. ERCP is a useful technique to clear the CBD pre-LC. However, ERCP in patients with biliary pancreatitis, but otherwise normal preoperative tests, has a low yield. In this group of patients, IOC is an appropriate alternative to pre-LC ERCP.

Adult↗
PubMed1991

Persistent hypomagnesemia following cisplatin chemotherapy in patients with ovarian cancer.

The development of acute hypomagnesemia following cisplatin administration is a well-recognized complication associated with the use of this chemotherapeutic agent. However, there is limited information available in the medical literature concerning how long this abnormality may persist following the discontinuation of cisplatin. Of 13 patients with ovarian cancer who had a baseline serum magnesium determination obtained prior to the initiation of a second-line cisplatin-based chemotherapy regimen, 9 (69%) were found to be hypomagnesemic (serum magnesium less than 1.4 mg/l), including 3 patients with serum magnesium values less than 1.0 mequiv/l. The median cisplatin-free interval for these 9 patients was 19 months (range 6-40 months). We conclude that persistent, and possibly permanent, hypomagnesemia is common following cisplatin chemotherapy.

Cisplatin↗
PubMed1991

Late effects of cisplatin-based chemotherapy on renal function in patients with ovarian carcinoma.

While the acute toxicity of cisplatin on renal function is well described, the long-term effects have received little attention in the medical literature. In an effort to examine this important issue, we evaluated the renal function of a group of 60 women with ovarian cancer who received a second-line cisplatin-based chemotherapy program at the Memorial Sloan-Kettering Cancer Center longer than 6 months following the completion of their initial cisplatin-based chemotherapeutic regimen. These patients had not received any cisplatin for a median of 19 months (range, 6-57 months) prior to beginning the second-line program. Only 4 patients (7%) had a serum creatinine value greater than 1.3 mg/dl (upper limit of normal in our laboratory) at the time of initiation of the second-line program. In each case, the serum creatinine was less than or equal to 1.6 mg/dl. An additional 6 patients (10%) had a greater than 50% increase in serum creatinine above the initial baseline value prior to any treatment, but were still within the normal range. Following second-line cisplatin therapy, only 1 of the 60 patients (2%) experienced a serum creatinine rise to greater than 2.0 mg/dl. We conclude that a limited number of patients with ovarian cancer who are long-term survivors following cisplatin-based chemotherapy exhibit evidence of a mild persistent compromise of renal function and, in general, second-line cisplatin can be administered to previously treated patients without the development of serious renal dysfunction.

Adult↗
PubMed1991

Second-line platinum therapy in patients with ovarian cancer previously treated with cisplatin.

In an effort to critically define the incidence and clinical characteristics of secondary responses to cisplatin-based therapy in patients with ovarian cancer previously treated with a cisplatin-based program, a retrospective review was undertaken of patients at the Memorial Sloan-Kettering Cancer Center who received greater than or equal to two cisplatin/carboplatin-based programs. Eighty-two patients were identified who met the entry criteria of having had a cisplatin-free interval (CFI) of more than 4 months between the completion of their first regimen and the institution of a second cisplatin/carboplatin program. Of the 72 assessable patients (10 had no measurable disease, and a laparotomy was not performed to assess response), 31 (43%) responded, including 10 surgically defined complete responses (S-CRs). The overall response rates (and S-CR rate), based on duration of CFI, were 5 to 12 months, 27% (5%); 13 to 24 months, 33% (11%); and more than 24 months, 59% (22%). Twenty-nine patients (35%) received noncisplatin/carboplatin-containing treatments between the cisplatin programs. Patients without any treatment for more than 24 months from the completion of their initial therapy experienced a 77% (17 of 22) response rate and a 32% (seven of 22) S-CR rate. In conclusion, secondary responses to cisplatin/carboplatin-based treatment are common in patients with ovarian cancer who have previously responded to the agents and increase in frequency with greater distance from the initial therapy.

Adult↗
PubMed1986

Cervical radiculopathy. A review.

This paper is a review of current information on cervical radiculopathy. The focus is on the natural history of the process, the accuracy of diagnostic tests to determine etiology, the differential diagnosis involved, and the surgical tactics available. The most important conclusions are the criteria for patient selection for surgery and a statistical demonstration of the adequacy of both the anterior and the posterior approaches for decompression of the cervical nerve root.

Humans↗