PubMed Health⌕ Search

Biomedical subjects

R Middleton

Publications and source records attributed to R Middleton.

At least 19 recordsLinked to original sources
PubMed1996

Identification of urinary benzodiazepines and their metabolites: comparison of automated HPLC and GC-MS after immunoassay screening of clinical specimens.

An automated high-performance liquid chromatographic method, benzodiazepines by REMEDi HS, was used to analyze benzodiazepines and their metabolites after beta-glucuronidase hydrolysis of 1-mL urine specimens from the following: 924 clinic and hospital patients whose specimens had previously been found to be presumptively positive using either EMIT or Triage immunoassay methodologies and 128 individuals whose specimens had screened negative by EMIT d.a.u.TM. REMEDi analyses did not correlate with the immunoassay results in 136 of the positive and three of the negative urine specimens. Gas chromatographic-mass spectrometric (GC-MS) confirmatory analyses were performed on these discordant specimens using 3 mL beta-glucuronidase-hydrolyzed urine followed by extraction with chloroform-isopropanol (9:1) and derivatization with N,O-bis(trimethylsilyl)trifluoroacetamide. Two benzodiazepines, flunitrazepam and clonazepam, and their 7-amino metabolites were analyzed without prior derivatization. The analyses established 87% concordance between REMEDi and GC-MS versus 13% concordance with immunoassay for the subset. GC-MS analysis of these 142 specimens demonstrated two reasons for the nonconcurrence between REMEDi and EMIT: EMIT had given either false-negative or false-positive results and EMIT had given a positive result even though the determined metabolites were below the 200-ng/mL cutoff for the immunoassay and the 80-ng/mL cutoff for REMEDi. A total of 23 specimens were found to contain only lorazepam by REMEDi and GC-MS, 15 of which had been screened by Triage. A reevaluation of these 23 specimens by EMIT d.a.u. demonstrated that 11 were positive. This finding was in contrast to previous reports that EMIT will not detect lorazepam glucuronide in urine. An unexpected finding was the REMEDi identification and subsequent GC-MS confirmation of 7-aminoflunitrazepam, a urinary metabolite of flunitrazepam that is not available in the United States and that represented illicit use by four patients. A distinct advantage of REMEDi proved to be its capability in identifying demoxepam, a major metabolite of chlordiazepoxide; GC-MS analysis could not detect this metabolite because of its thermal decomposition to nordiazepam. To further evaluate the specificity of REMEDi, we conducted GC-MS analyses in a random fashion on 55 additional nondiscordant urine specimens that were identified as either positive or negative, as well as 22 specimens identified as containing 7-aminoclonazepam by REMEDi. Concurrence was observed between the two methods for all specimens, with the exception of one apparent false positive for alpha-hydroxyalprazolam by REMEDi. The reproducibility of the REMEDi method was found to be excellent; it was assessed by comparing results of 266 specimens that were reprocessed in different batches and for known calibrators and controls also processed with each batch. Study results demonstrated that the automated REMEDi assay for urinary benzodiazepines and their metabolites was comparable with GC-MS but had distinct advantages over GC-MS because of the following reasons: simplicity of the assay, less time required for analyses, and provision of additional information concerning the parent benzodiazepine.

1-Propanol↗
PubMed1996

The influence of osteoarthritis on the pattern of proximal femoral fractures.

The relationship between subcapital and trochanteric fractures and osteoarthritis was investigated to test the hypothesis that the presence of osteoarthritis would predetermine the site of the fracture. The authors reviewed 429 pelvic radiographs of patients with proximal femoral fractures. Osteoarthritis was found in 18 patients (4.2%). Sixteen patients followed the predicted fracture pattern of subcapital fracture and osteoarthritis of the other hip, or trochanteric fracture and osteoarthritis of the same hip. These results were statistically significant, supporting the hypothesis that patients with osteoarthritis of the hip who fall are likely to sustain a contralateral subcapital fracture or an ipsilateral trochanteric fracture.

Hip Fractures↗
PubMed1995

Diagnostic studies with intravenous and intranasal growth hormone-releasing peptide-2 in children of short stature.

GH secretion is primarily regulated by the hypothalamic-releasing hormones GHRH and somatostatin. Additionally, several neurotransmitters act at the hypothalamus and pituitary to modulate GH release. The agents commonly used in clinical practice to diagnose GH deficiency, such as arginine, insulin and L-dopa, act through the neural GH network. Many children with a poor GH response to conventional agents have a significant serum GH response to iv GHRH. GH-releasing peptides (GHRPs) are synthetic peptides that like GHRH act directly on pituitary somatotrophs to stimulate GH release. GHRP-2, an investigational drug, is one of the most potent members of the GHRP family. It has been shown to be effective in adults via the oral and intranasal as well as the iv route of administration. In this study, GH responses to GHRP-2 were compared with GH responses to other provocative agents in children of short stature. GHRP-2 was administered iv or intranasally to children with short stature. In the same subjects, GHRP-2 was administered iv in combination with GHRH. Twenty-four children undergoing evaluation for GH deficiency received at least one conventional agent (arginine, L-dopa/exercise, insulin) in addition to iv GHRH and GHRP-2. The GH responses to GHRH or GHRP-2 were similar in each child, and both were equally reliable predictors of pituitary reserve. The conventional agents used in GH testing were less likely to predict the capacity of the pituitary to release GH than were either GHRH or GHRP-2. There was no correlation between maximal GH response to standard tests with GH responses to GHRH or GHRP-2. A subset of the group of 21 children who had a robust response to iv GHRP-2 were later administered GHRH+GHRP-2 simultaneously. The GH response to GHRH+GHRP-2 was synergistic in this group of 12 children, similar to previously reported observations in adults of normal stature. Fifteen of the 21 children who had a robust response to the iv GH-releasing factors also received intranasal GHRP-2. All 15 of these children had a significant GH response to intranasal GHRP-2 over a dose range of 5-20 micrograms/kg per dose. The mean peak GH response to 15 micrograms/kg was 31.3 micrograms/L. The intranasal preparation was well tolerated.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Intranasal↗
PubMed1994

Tissue disposition of 26aluminum in rats measured by accelerator mass spectrometry.

A trace quantity of 26aluminum (26Al) was administered intravenously to 1 normal and 1 uremic rat. After a 3-week period, the animals were sacrificed and samples of bone, muscle, kidney, liver, heart, and brain were analyzed for their 26Al content. In the normal and uremic rats, most of the tissue 26Al was found in bone amounting to 0.9% and 2.0%, respectively, of administered dose/g dry weight of tissue. Much smaller amounts of isotope were found in the other tissues in both animals. In the normal rat, the descending order of 26Al content in other tissues was: kidney, 0.2% > liver, 0.06% > heart, 0.03%, > brain and muscle, 0.02%. In the uremic rat, the same order of tissue 26Al content was found with kidney, 0.37% > liver, 0.06% > heart, 0.02% > brain and muscle, 0.01% per g dry weight of tissue. When expressed per g wet weight of tissue in the 2 animals, a similar order of tissue 26Al content was found. In comparing the amount of 26Al in the bone of the 2 rats, the uremic animal was found to have more than twice that found in the bone of the normal rat when expressed either per g dry or wet weight of bone. However, 26Al content of other tissues was similar in the 2 animals. This suggests that uremic bone may have a greater affinity for aluminum than normal bone, but kidney, liver, brain, heart, and muscle appear to behave similarly in uremic and normal rats in regard to incorporation of a single trace dose of isotope in the 3-week time frame of the present study.

Aluminum↗
PubMed1992

Comparison of four methods for assessing airway bacteriology in intubated, mechanically ventilated patients.

A prospective evaluation of lower airway bacteriology from intubated, mechanically ventilated patients was performed by comparing the qualitative and quantitative recovery of bacteria using four different techniques. Twelve intubated, mechanically ventilated patients who satisfied accepted clinical criteria for the suspicion of ventilator-associated pneumonia were studied. Airway secretions were obtained from each patient by: (1) blind endotracheal aspiration (ET); (2) Accu-cath pulmonary culture catheter (Accu); (3) bronchoscopic protected specimen brush (BPSB); and (4) bronchoalveolar lavage (BAL). ET specimens were cultured semi-quantitatively (1+ to 4+) aerobically, and all other specimens were cultured quantitatively both aerobically and anaerobically. The BPSB recovered 9 organisms in > or = 10(3) colony forming units/ml, a standard number often used to indicate significant growth. Of these 9 organisms, 7 were recovered at > or = 10(3) cfu/ml by Accu, and 6 were recovered at > or = 10(4) cfu/ml by BAL. All 8 aerobic isolates recovered in > or = 10(3) cfu/ml by BPSB also were recovered by ET aspirate. Five of these were recovered in > or = 3+ semi-quantitative growth by ET aspirate. Of 30 organisms recovered in < 3+ semi-quantitative growth by ET aspirate, 28 were recovered in < 10(3) cfu/ml by BPSB, indicating a negative predictive value of 93%. Thus, it appears that these four methods provide reasonably similar qualitative and quantitative recovery of bacteria from the lower airways of intubated, mechanically ventilated patients. In addition, routine Gram's stain and semi-quantitative aerobic culture of endotracheal aspirate may provide useful information in patients with suspected ventilator-associated pneumonia.

Bacteria↗
PubMed1992

[Beta-ketothiolase deficiency: a case of ketoacidosis with hyperglycinemia].

Regarding a case of beta-ketothiolase deficiency revealed by ketoacidosis with hyperglycinemia, the authors show the way to diagnose and to treat this disease. Ketoacidosis without hyperglycemia or lactacidemia suggested this diagnosis. Gas chromatography-mass-spectrography revealed unusual urinary excretion of metabolic products of isoleucine. The enzymological study of fibroblasts confirmed the diagnosis. The treatment of acute episodes consisted of acidosis control and exclusive glucides intake before diagnosis. Afterwards, a controlled proditic diet and L-carnitine must be given and fasting must be avoided.

Acetyl-CoA C-Acyltransferase↗
PubMed1991

Accelerator mass spectrometry: application to study of aluminum kinetics in the rat.

The advent of accelerator mass spectrometry (AMS) now permits the ultrasensitive detection of extremely long-lived isotopes, including 14C, 26Al, and 41Ca. Until now, tracer studies of aluminum kinetics have not been possible because aluminum has only two isotopes, with half-lives of 6.5 min (29Al) and 7 x 10(5) yr (26Al), neither of which is suitable for conventional studies. In a novel experiment we have employed AMS to study aluminum kinetics in a normal rat and a 5/6-nephrectomized rat over a 3-wk period of intravenous injection of a tracer dose of 26Al. Kinetics were similar in the two animals; approximately 75% of intravenously injected tracer 26Al was excreted in the urine in the first 24 h as was approximately 80% after 3 wk. Renal clearance of 26Al was approximately 0.75 ml.min-1.kg body wt-1 in both rats. The results clearly demonstrate the potential of this technique for isotope tracer studies in animals as well as in humans.

Aluminum↗
PubMed1991

Tuberculous pleural effusion. Twenty-year experience.

We reviewed the records of 1,738 cases of tuberculosis seen during the period from 1968 to 1988 in Mobile, Alabama. Seventy cases of tuberculous pleural effusion were identified and constituted 4.9 percent of all disease due to Mycobacterium tuberculosis during this period. Tuberculous pleural effusion was diagnosed if the patient had M tuberculosis cultured from sputum, pleura, or pleural fluid and had a roentgenographic pleural effusion without an alternative explanation for the presence of the effusion. The diagnosis of tuberculous pleural effusion was made in the absence of a positive culture if the patient had an undiagnosed lymphocytic exudative pleural effusion and all clinical and roentgenographic abnormalities resolved on antimycobacterial chemotherapy. The mean age of all patients was 47 +/- 18.4 years. The 70 cases were evenly divided between 35 that were accompanied by roentgenographic pulmonary parenchymal infiltrates and 35 that occurred in the absence of parenchymal infiltrates. We conclude that cultures of all potentially diagnostic specimens (sputum, pleural fluid, and pleura) and an intermediate-strength skin test, are sensitive tests for the diagnosis of tuberculous pleural effusion. In addition, the age of patients with tuberculous pleural effusion appears to be increasing.

Adult↗
PubMed1985

Familial osteochondritis dissecans: a dysplasia of articular cartilage?

Two cases of osteochondritis dissecans in a boy and his mother are described. In the son only the knee and elbow joints and the epiphysis of the right second metacarpal were involved, whereas the mother showed early generalised degenerative joint disease associated with many large loose bodies in one knee. The authors speculate that familial osteochondritis dissecans is a dysplasia of articular cartilage caused by abnormal chondrocyte metabolism.

Adult↗
PubMed1985

Advanced carcinoma of the nasopharynx. 2. Pattern of failure in 256 patients.

Of 256 patients with advanced carcinoma of the nasopharynx, 82% presented with Stage IV disease. The 5-year survival was 15% with 83% failing within 2 years. Prognosis was related to stage (p less than 0.03), neck status (p less than 0.03), initial performance status (p less than 0.001) and radiation dose (p less than 0.003). With no pathological neck glands (N0), less than 5% failed radiotherapy. Overall, 36% had distant metastases, correlating with the N Stage (p less than 0.001) but not with the T Stage. The most frequent site of metastasis was lung, then bone and liver. Radical neck dissection failed to increase tumor control, contributing to three fatal complications. New radiotherapeutic regimens have so far failed to substantially improve the results.

Adult↗
PubMed1983

Cis-platinum induction chemotherapy in the multi-modality initial treatment of advanced stage IV carcinoma of the head and neck.

Twenty-eight previously untreated patients with unresectable and radical radiotherapy incurable advanced stage IV squamous cell carcinoma of the head and neck underwent cis-diamminedichloroplatinum (DDP) induction chemotherapy followed by radiation with 6500 rad to the primary and 5000 rad to the supraclavicular area given over six weeks. Of the 26 patients completing this regimen, none had a complete remission after DDP alone. Following radiation therapy, 39% of the patients had a total regression of all disease. This modality converted 16 patients to operable candidates. After surgery, 68% of the patients were in complete remission. Survival was significantly correlated (P less than or equal to 0.001) with complete disappearance of disease, and surgical intervention was additive to chemotherapy and radiation. Histopathologic staging demonstrated that clinical assessment of residual disease in the neck determined after chemotherapy and radiation of the neck was unreliable. Therefore, radical neck dissection appears indicated in lesions initially staged as N2 and N3 irrespective of the postradiation clinical status of the neck region. Finally, a serious limitation of improved survival duration was the occurrence of disseminated disease in patients whose primary and regional lesions were well controlled.

Carcinoma, Squamous Cell↗
PubMed1982

Advanced carcinoma of the nasopharynx. A clinical study of 274 patients.

A total of 274 patients with a diagnosis of nasopharyngeal carcinoma was treated in eight Veterans Administration Hospitals over a period of 22 years. Of the 274 patients, 256 (93%) had squamous-cell carcinoma, while 18 (7%) had other tumors. Most of the squamous-cell carcinoma patients (82%) had Stage IV disease; cervical lymph node metastases were found in 193 (75%), and distant metastases were present in 22 (9%). The actuarial 5-, 10-, and 15-year survival rates for the 256 squamous-cell carcinoma patients were 15%, 10%, and 7%, while they were 49%, 42%, and 35% for the 18 patients with other tumors (p = 0.006). There was a progressive decrease in 5-year survival with the increase in the stage of tumor. The survival of the 63 patients without metastases was better than the survival of the 193 patients with cervical metastases (24% vs. 12% at 5 years, p = 0.03). The presence of T4 disease or Initial Performance Status of less than 80 on the Karnofsky Scale indicated a poor prognosis (p = 0.0001). Treatment failure occurred in 83% of the patients by 2 years after therapy and was due to the lack of tumor control at the primary site. Advanced (N3) cervical lymph node metastases indicated that systemic tumor dissemination of the nasopharynx is an uncommon malignancy.

Adult↗
PubMed1981

Mandibular and para-mandibular tumors in children. Report of 16 cases.

Sixteen cases of mandibular tumors or paramandibular soft tissue tumors with mandibular involvement are reported. These include such rare mandibular tumors or tumor-like conditions as melanotic progonoma, intraosseous haematoma secondary to von Willebrand's disease, post-irradiation osteosarcoma, monostotic eosinophilic granuloma, aneurysmal bone cyst and osseous hemangiopericytoma. Three cases of cherubism, one of fibrous dysplasia or aggressive fibromatosis and one of central giant cell reparative granuloma are also reported. The soft tissue tumors comprise round cell sarcoma, parotid adeno-carcinoma with generalised metastases, embryonal rhabdo-myo-sarcoma, neuro-fibro-sarcoma and congenital cystic hygroma. In all the cases the disease was well advanced when the patient presented for X-ray examination. The specific X-ray diagnosis of mandibular and paramandibular tumors in childhood is more difficult than that of similar tumors in other parts of the body.

Adolescent↗