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Biomedical subjects

A R Miller

Publications and source records attributed to A R Miller.

At least 19 recordsLinked to original sources
PubMed1992

Simultaneous use of two retroviral vectors in human gene marking trials: feasibility and potential applications.

Two Moloney murine leukemia virus (Mo-MLV)-based neoR retroviral vectors--LNL6 and G1Na--were used to transduce various human tumor-infiltrating lymphocytes (TIL) populations. These groups included bulk CD(8+)- and CD(4+)-enriched TIL from human renal cell carcinomas and melanomas. Transduction efficiencies averaged 5% for single 4-hr supernatant infections. Integrated provirus could be detected for up to 4 weeks of in vitro culture. LNL6 provirus could be distinguished from G1Na provirus using specific polymerase chain reaction (PCR) primers. A single neomycin phosphotransferase (neoR) gene copy could be detected in 10(5) TIL. Using quantitative PCR, the relative ratio of LNL6 to G1Na copies in the same sample could be determined even at low copy numbers. These preclinical studies demonstrate the feasibility of using two retroviral marking vectors in human gene therapy efforts.

Base Sequence↗
PubMed1992

The surgical spectrum of hereditary pancreatitis in adults.

The role of operative intervention for hereditary pancreatitis, a rare form of chronic parenchymal destruction, is unclear. To determine whether surgical therapy is safe and provides prolonged symptomatic relief, the authors reviewed the management of 22 adults (11 men, 11 women) with hereditary pancreatitis treated surgically between 1950 and 1989. Hereditary pancreatitis was defined as a family history of two or more relatives with pancreatitis and clinical, biochemical, or radiologic evidence of pancreatitis. The mean ages at onset of symptoms and at operation were 15 years (range, 3 to 52 years) and 31 years (range, 18 to 54 years), respectively. Pain was the primary indication for operation in all patients. Additional symptoms included nausea, vomiting (73%), weight loss (55%), and diarrhea (41%). Ductal dilatation was present in 68%, pancreatic parenchymal calcifications in 73%, pseudocysts in 36%, and splenic vein thrombosis in 18%. Primary operations included ductal drainage in 10 patients, pancreatic resection alone in three, resection with drainage in three, cholecystectomy plus sphincteroplasty in two, cholecystectomy with or without common bile duct exploration in two, pancreatic abscess drainage in one, and pseudocyst drainage in one. There were no perioperative deaths, and the morbidity rate was 14% (intra-abdominal abscess, wound infection, and urinary tract infection). Symptoms recurred in nine patients. Severity prompted reoperation in five. Secondary operations included pancreatic resection in three, pseudocyst excision in one, and pancreaticolithotomy in one. Follow-up to date is complete and extends for a median of 85 months. Eighteen patients (82%) are clinically improved or asymptomatic. Symptoms have persisted in four patients, and two patients have died of pancreatic carcinoma. Two patients died of unrelated causes. Surgical therapy for patients with hereditary pancreatitis selected on the basis of the traditional indications for surgical treatment of chronic pancreatitis is safe and efficacious.

Adult↗
PubMed1992

Postoperative radiographs as predictors of clinical outcome in unstable ankle fractures.

This study reviews a group of 80 consecutive displaced ankle fractures treated operatively and followed for an average of 3.2 years. Fractures included bone or combined bone and ligamentous injuries in which the initial talar displacement was greater than or equal to 2 mm. The immediate postoperative roentgenograms were examined for several features, which included widening of the syndesmosis, fibular length, talo-crural angle, talar tilt, presence and size of a posterior malleolar fracture, and an abnormality of the medial clear space. Patients were examined at follow-up per Cedell, and their clinical evaluations were correlated with the analysis of radiographic features and demographic data. Good to excellent results were seen in 80% of the cases. The radiographic factors most predictive of a poor outcome were abnormal medial clear space and the presence of a large (greater than 20%) posterior malleolar fracture (p less than 0.05). Fibular shortening, talar tilt, and syndesmotic widening suggested a poor result, but these findings were not statistically significant. Multiple (two or more) radiographic abnormalities correlated with a poor prognosis. Conversely, a perfect radiographic result did not guarantee an excellent clinical outcome. Older patients and those with a delay between injury and surgery greater than 7 days tended to have a poorer result.

Adolescent↗
PubMed1992

Depletion of neuroendocrine cells in rectal biopsy specimens from HIV positive patients.

AIMS: To compare the density of neuroendocrine cells in rectal biopsy specimens from human immunodeficiency virus (HIV) infected individuals with that of a control group. METHODS: Neuroendocrine cells in rectal biopsies were identified using an immunohistochemical stain for chromogranin and subsequently quantified using a method of linear intercept. RESULTS: Neuroendocrine cells were found to be significantly decreased in the HIV positive group. CONCLUSIONS: Loss of neuroendocrine cells may contribute to apoptotic bodies seen in this condition. This could be related to infection of these cells with HIV and could contribute to diarrhoeal disease in HIV infection.

Biopsy↗
PubMed1991

Infantile colic. Is it a gut issue?

Despite its salience in terms of both prevalence and distress occasioned in parents, the nature and causes of infantile colic remain poorly understood. Causes in the gut (abnormal sensitivity to dietary components, excessive gas, intestinal hypermotility, hormonal factors) and alternative explanations (variant of normal crying behavior, effect of atypical parenting, manifestation of problems in parent-infant interaction) are critically reviewed. Gut pathology may, at best, explain a minority of cases. Although evidence in support of both sets of causes exists, it is frequently undermined by methodologic limitations, notably inadequate definition of the subjects studied. Conceptual issues have also constrained progress in resolving some of the dilemmas, specifically the assumption that gut and non-gut causes are mutually exclusive, and that presence of symptoms necessarily implies abnormalities of function. It is proposed that (1) colic may not be a homogeneous group, but a loose description for the crying of various clinical and etiological subgroups; and (2) that most cases may be conceptualized as resulting from behavioral and biologic interactions in which both the behavioral and biologic factors are functioning normally rather than pathologically.

Colic↗
PubMed1991

Simultaneous bilateral hernia repair. A case against conventional wisdom.

The timing of bilateral hernia repair remains controversial. Because of reported high recurrence rates after simultaneous bilateral repair, staged procedures have been suggested. This study determined recurrence and complication rates of unilateral versus simultaneous bilateral repair. Of 659 patients undergoing hernia repair between 1974 and 1980, 333 underwent unilateral repair and 329 had simultaneous bilateral repair. More than 90% of patients were followed until death or a minimum of 60 months (median, 104 months). Perioperative complications were associated with 18% of repairs. More morbidity occurred in the bilateral group. However complication rates for specific events were not significantly different, except for urinary retention, which occurred in 20 patients (6.1%) of the unilateral group and 49 (15%) of the bilateral group (p less than 0.001). Overall 25 recurrences occurred in the unilateral group and 31 in the bilateral group. Recurrence rates at 5 and 9 years were, respectively, 4.8% and 8.8% in the unilateral group and 5.0% and 9.1% in the bilateral group (p = 0.861). These data suggest that simultaneous bilateral inguinal herniorrhaphy does not result in increased rates of most postoperative complications or recurrence when compared with unilateral repair.

Female↗
PubMed1991

Autonomic denervation in jejunal mucosa of homosexual men infected with HIV.

Autonomic nerves in jejunal mucosa of HIV-infected patients show severe structural damage on electron microscopic examination. The aim of this study was to quantify loss of autonomic axons from the lamina propria of HIV-infected patients in different clinical stages of disease. Jejunal biopsies were taken from 19 HIV-antibody-positive homosexual men and from 10 control patients. Autonomic fibres in the mucosa were stained with a neurone-specific polyclonal antibody, PGP 9.5. The density of axons was quantified by a point-counting technique using a Lennox eyepiece graticule under light microscopic examination. There was significant reduction in axonal density in the villi of HIV-infected patients [mean, 9.0; standard deviation (s.d.), 4.7] compared with controls (mean, 15.3; s.d., 5.2; P = 0.003), and in the pericryptal lamina propria of HIV-infected patients (mean, 17.8; s.d., 5.4) compared with controls (mean, 27.3; s.d., 6.2; P = 0.0002). Although autonomic denervation occurs throughout the jejunal mucosa of HIV-infected patients, there was no correlation between the clinical stage of HIV disease and the degree of denervation. The denervation was greatest in patients with the most severe diarrhoea, but this difference was not significant. This study provides the first quantitative morphological evidence for depletion of autonomic nerves in the jejunum of patients infected with HIV. Autonomic neuropathy may contribute to chronic diarrhoea in HIV disease.

AIDS-Related Complex↗
PubMed1990

A cystoscopically directed biopsy technique developed in canine pancreaticoduodenal transplantation.

Present methods of monitoring for allograft dysfunction in pancreaticoduodenal transplantation (urinary amylase, scintigraphy) give indirect evidence and do not consistently allow recognition of early, potentially reversible rejection from other causes of allograft dysfunction. For better diagnosis of allograft dysfunction, adequate tissue specimens must be obtained without trauma to the allograft. We devised a cystoscopically directed needle biopsy technique to obtain tissue from the canine pancreaticoduodenal allograft. This technique is made feasible by a duodenocystostomy similar to that in human pancreaticoduodenal transplantation. The duodenum acts as a port of entry for the biopsy instruments, providing access to the pancreas. A 24F side-viewing nephroscope is used to view the duodenum. The tissue specimen is obtained with an 18-gauge, 350 mm Menghini aspiration needle inserted by way of the nephroscope through the duodenum and into the pancreas. Pancreaticoduodenal allotransplantation with a duodenocystostomy for exocrine drainage was performed in 18 dogs. Of 59 serial biopsy specimens obtained, 41 (69.5%) were adequate for pathologic evaluation. The principal complication associated with the technique was minimal bleeding at the biopsy site, occurring in 22 of the 59 biopsy procedures. This cystoscopically directed biopsy technique appears to be safe, often obtains adequate tissue for diagnosis, and may be directly applicable for distinguishing causes of allograft dysfunction in human pancreaticoduodenal transplantation.

Animals↗
PubMed1989

Diversion of the gastroduodenal vein: an in situ model of systemic insulin drainage.

A technique of diversion of the gastroduodenal vein in a canine model is described to compare long-term metabolic effects of systemic versus portal pancreatic endocrine drainage. The vein was transected at its entrance into the portal vein and either diverted to the inferior vena cava (systemic group) or reanastomosed to the portal vein (portal group). All remaining venous drainage of the pancreas was interrupted. An additional group of animals underwent laparotomy without manipulation of pancreatic vasculature (sham group). Fasting peripheral insulin and glucose values were determined 3 months postoperatively. Fasting insulin values were significantly higher in the systemic group (mean 10.7 +/- 1.06 U/ml) than in the portal (5.8 +/- 0.70, P = 0.002) and sham (6.4 +/- 0.68, P = 0.01) groups. Fasting glucose values were not significantly different in the three groups. At sacrifice, venous thrombosis was noted in one systemically diverted dog (6.7%). All other anastomoses were patent. No significant collateralization was apparent in any group. No significant complications were noted. This procedure simulates the hormonal milieu created by heterotopic pancreatic transplantation while preserving pancreatic innervation and exocrine function, and serves as an excellent model for investigating the effects of systemic hyperinsulinemia on protein, carbohydrate, and lipid metabolism.

Animals↗
PubMed1989

The distribution of wearout over evolved reliability structures.

A multiple-integral equation, termed the wearout equation, describes the distribution of wearout (or aging) over evolved reliability structures, such as organisms and self-replicating machines, and thus statistically governs virtually all aging properties of the systems. The equation is applied to the computation of ab initio ("from the beginning") life tables for four natural populations of ungulates--wild boar, Dall sheep, African buffalo, and hippopotamus--which represent a broad range of survival characteristics. The good agreement of the ab initio and empirical tables, the best available for testing the theory, demonstrates the basic realism of the wearout equation. If the equation withstands further experimental testing, its analysis may provide insight into fundamental questions in the biology of aging.

Aging↗
PubMed1989

Pleuropulmonary actinomycosis associated with a systemic-to-pulmonary artery fistula and contralateral metastatic back mass.

We report a case of systemic-to-pulmonary artery fistula associated with thoracic actinomycosis and with metastatic hematogenous dissemination to the soft tissues of the back. The difficulty in diagnosing thoracic actinomycosis may predispose to the increased incidence of hematogenous spread of this disease. Although resection of pulmonary tissue including the infectious mass was required in previous cases, resection of the pleural mass alone was curative in this patient when combined with penicillin therapy.

Abscess↗
PubMed1989

Sequential histopathologic changes in pancreaticoduodenal allograft rejection in dogs.

To determine the nature and sequence of the histologic changes in the early rejection of pancreaticoduodenal allografts and to assess the correlation between pancreaticoduodenal biopsy findings and the pathologic changes in the graft, we performed serial cystoscopically directed needle biopsies of pancreaticoduodenal allografts in 18 dogs and compared the findings with the histologic changes in 16 autografts as controls. Tissue adequate for evaluation was obtained by the biopsy technique in 70% of instances. The earliest and most characteristic manifestation of rejection was diffuse mixed inflammatory infiltrates involving the pancreatic acinar tissue and duodenum. The biopsy findings correlated well with the changes in the resected pancreatic specimens. Cellular rejection in the duodenum correlated with rejection in the pancreatic graft. There were no changes in the autografts that resembled cellular rejection. We conclude that, in the canine model, cystoscopically directed needle biopsy of pancreaticoduodenal allografts consistently provides adequate tissue for the diagnosis of rejection; the status of the graft can be monitored by serial biopsies of pancreatic acinar tissue and, possibly, by serial biopsies of the duodenal wall alone.

Animals↗
PubMed1989

Jejunal enteropathy associated with human immunodeficiency virus infection: quantitative histology.

Jejunal biopsy specimens from 20 human immunodeficiency virus (HIV) positive male homosexual patients were analysed and compared with those of a control group to determine whether the abnormalities were caused by the virus or by opportunistic infection. The degree of villous atrophy was estimated with a Weibel eyepiece graticule, and this correlated strongly with the degree of crypt hyperplasia, which was assessed by deriving the mean number of enterocytes in the crypts. The density of villous intraepithelial lymphocytes fell largely within the normal range, either when expressed in relation to the number of villous enterocytes or in relation to the length of muscularis mucosae. Villous enterocytes showed mild non-specific abnormalities. Pathogens were sought in biopsy sections and in faeces. Crypt hyperplastic villous atrophy occurred at all clinical stages of HIV disease and in the absence of detectable enteropathogens. An analogy was drawn between HIV enteropathy and the small bowel changes seen in experimental graft-versus-host disease. It is suggested that the pathogenesis of villous atrophy is similar in the two states, the damage to the jejunal mucosa in HIV enteropathy being inflicted by an immune reaction mounted in the lamina propria against cells infected with HIV.

Acquired Immunodeficiency Syndrome↗