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Biomedical subjects

I Thompson

Publications and source records attributed to I Thompson.

At least 19 recordsLinked to original sources

An unusual presentation of an encephalocele to the otolaryngologist.

An unusual case of encephalocele causing obstruction of the upper airway in a neonate is described. The patient presented with a large mass in the neck, which extended from the base of the skull to the level of the larynx. Although there was no evidence of a defect of the skull base, subsequent excision and histological examination confirmed an encephalocele.

Airway Obstruction

A conserved domain for glycogen binding in protein phosphatase-1 targeting subunits.

The skeletal muscle glycogen-binding subunit (GM) of protein phosphatase-1 (PP1) is the founding member of a family of proteins that tether the PP1 catalytic subunit (PP1C) to glycogen and promote the dephosphorylation of glycogen synthase. A hydrophobic sequence (called here the VFV motif) is conserved among GM, the liver subunit GL, and the widely expressed subunits, PTG, R5 and U5. This study analyzed the role of this VFV motif in binding to glycogen and PP1C. Glutathione S-transferase (GST) fusions with the N-terminal domain of GM (GST-GM(1-240)) and with the full length R5 protein (GST-R5) both bound to glycogen in a co-sedimentation assay. In contrast, GST itself did not bind to glycogen. A single residue substitution in GST-GM(1-240), F155A, reduced glycogen binding by 40%. Double residue substitutions V150A/F155A and F155A/V159A resulted in greater reductions (60-70%) in glycogen binding, showing these hydrophobic residues influenced the protein-glycogen interaction. The wild type and V150A/ F155A fusion proteins were digested by trypsin into the same sized fragments at the same rate. Furthermore, the wild type and mutated GST-GM proteins as well as GST-R5 bound equivalent amounts of PP1C, in either pull-down or far-Western assays. These results demonstrated retention of overall tertiary structure by the mutated fusion proteins, and indicated that glycogen and PP1C binding are independent of one another. A 68 residue segment of R5 encompassing the VFV motif was sufficient to produce glycogen binding when fused to GST. This motif, that is in bacterial and fungal starch metabolizing enzymes, probably has been conserved during evolution as a functional domain for binding glycogen and starch.

Amino Acid Sequence

High grade prostatic intraepithelial neoplasia in military working dogs with and without prostate cancer.

BACKGROUND: High grade prostatic intraepithelial neoplasia (PIN) is the most likely precursor of human prostate cancer and is commonly found in men undergoing prostatic needle biopsy for suspected cancer. Recent work has demonstrated that pet dogs, like humans, develop PIN spontaneously and in association with prostate cancer. Pet dogs are the most domesticated animal, sharing the habitat and oftentimes the diet of their owners. If PIN and prostate cancer are strongly related to environmental factors, then the prevalence of these findings might differ in a population of dogs such as military working dogs which is not exposed to the habitat and diet of humans. In this study, we determined the prevalence of PIN in prostates of aged military working dogs with and without prostatic adenocarcinoma. METHODS: Cases were selected from the military working dog slide and tissue archive at the Armed Forces Institute of Pathology, Washington, DC. The most recent 329 necropsies (1991 to 1996) were examined histologically by multiple reviewers; of these, 199 dogs (60%) were found to have evaluable prostatic tissue. In addition, the most recent 50 necropsies (1958 to 1996) with the diagnosis of prostatic cancer were examined, of which 25 cases (50%) were found to have evaluable prostatic adenocarcinoma. In most cases, a single large transverse section of prostatic tissue was available for review. Medical records for each dog were reviewed independently, and age, clinical history, indications for euthanasia, and other health problems were recorded. RESULTS: High grade PIN was identified in 3% of dogs (6 of 199 dogs) without prostate cancer. A total of 50.8% of dogs in this study group (101 of 199 dogs) were known to be sexually intact, 26.7% of dogs (53 of 199 dogs) were castrated, and the status of the remaining 22.6% of dogs (45 of 199 dogs) was unknown. High grade PIN was present in 18 of 25 dogs (72%) with prostatic adenocarcinoma. Of these cases, 11 dogs (44%) were castrated, 4 dogs (16%) were intact, and the status of 10 dogs (40%) dogs was unknown. Gleason scores ranged from 6 to 10, with a mean of 8.4 and a median of 8. CONCLUSIONS: High grade PIN is present in a small but substantial number (3%) of military working dogs. Of military working dogs with prostatic adenocarcinoma, 72% had high grade PIN. The true prevalence in each of these cohorts is likely to be higher given the sampling variation inherent in evaluating a single random histologic section. Aged male dogs seem to have substantial clinical utility as an animal model for prostatic carcinogenesis. We recommend that serial sectioning and total embedding of the prostate should be used to more thoroughly characterize premalignant and malignant diseases in aged military working dogs. This method will provide important data to determine whether a model of spontaneous PIN in elderly dogs may have clinical utility in developing strategies directed toward preventing and treating prostate.

Adenocarcinoma

Maternal recognition of foetal infection with bovine virus diarrhoea virus (BVDV)--the bovine pestivirus.

BACKGROUND: Pestiviruses are the veterinary viruses with genome homology to human hepatitis C virus (HCV). This group includes classical swine fever virus (CSFV), border disease virus of sheep (BDV) and bovine virus diarrhoea virus (BVDV). There are some similarities in the pathology of all three virus infections; in utero transmission to the foetus can cause early embryonic losses, severe congenital abnormalities and, particularly with BVDV, lifelong persistent infections. In situ hybridisation studies have demonstrated virus within reproductive tissues and the germinal centres of lymphoid tissue. OBJECTIVES: To examine the immune response of cattle throughout their pregnancy following infection with bovine pestivirus (BVDV) during the first trimester (before 110 days). STUDY DESIGN: In two experimental studies, heifers were infected with BVDV before 98 days gestation. Their antibody response was monitored during the remainder of the pregnancy. In another study, the antibody response of pregnant cattle was monitored following a natural infection of BVDV on a farm. Calves of the dams from all these three studies were examined, following birth, for persistent BVDV infection. RESULTS: It was observed that in dams carrying persistently infected foetuses, the immune response was markedly higher (13811 + 1273 U ELISA antibody) than in those dams carrying uninfected foetuses (2542+/-588 U ELISA antibody). These results were used to establish an antibody threshold (10000 U ELISA antibody) to predict the virus status of unborn calves during a farm outbreak of BVDV infection. The combined results of experimental and farm studies showed that in dams with low antibodies, 5/15 calves were infected whereas in dams with high antibodies, 17/19 calves were infected. CONCLUSIONS: The predictive reliability of the assay appeared valuable but not secure. The ability of BVDV to infect the foetus with consequent maternal recognition, whilst remaining inaccessible to maternal immune exclusion, is a novel finding.

Abortion, Veterinary

Army and Air Force leadership in the Prostate Cancer Prevention Trial.

Prostate cancer is now the most common solid tumor in men in the United States. Although the current public health approach to this disease is early diagnosis and treatment, investigations are also focusing on the possibility of disease prevention. The Prostate Cancer Prevention Trial, begun in 1993, has completed recruitment of 18,000 men who will be randomized to receive either finasteride or placebo to determine if finasteride can prevent the development of this disease. Both Army and Air Force institutions are participating in this trial, with four Department of Defense institutions contributing over 10% of the patients randomized. The results of this study may have a major impact on active duty personnel for whom prevention of prostate cancer may become possible.

Enzyme Inhibitors

Prostate rebiopsy is a poor surrogate of treatment efficacy in localized prostate cancer.

PURPOSE: Many investigators use prostate rebiopsy as an indicator of treatment efficacy and tumor response of localized prostate cancer for therapies in which the gland remains in situ. Because of the inherent sampling error of needle directed biopsies, however, some men will have a false-negative rebiopsy even if they have had no therapy or if the therapeutic intervention was unsuccessful in eradicating the malignancy. We evaluate the risk of a false-negative biopsy and the clinical factors that influence this risk. MATERIALS AND METHODS: A total of 90 patients undergoing radical prostatectomy for clinically localized disease underwent sextant biopsy of the prostate immediately after removal of the gland. Data collected included prostate specific antigen (PSA), hormonal status, age and biopsy core status. RESULTS: Of the total study population 67.8% received neoadjuvant hormonal therapy. While all patients had pathologically confirmed adenocarcinoma within the prostatectomy specimen, 45.6% demonstrated a false-negative rebiopsy. Within a combined predictive model, PSA and hormonal status demonstrated a statistically significant effect on the false-negative rebiopsy rate. Predictive power of this combined model was high across the spectrum of risk for a false-negative rebiopsy. CONCLUSIONS: This series demonstrates that the risk of a false-negative sextant biopsy in the presence of documented prostate cancer is high and is affected by several factors, including PSA and hormonal status. These data suggest that prostate sextant rebiopsy is an inaccurate method of assessing the therapeutic efficacy of treatments for carcinoma of the prostate in which the gland remains in situ following therapy.

Adenocarcinoma

Clotting parameters in patients with adolescent idiopathic scoliosis undergoing posterior spinal fusion and instrumentation.

Thirty-six patients, 9 males and 27 females, average age 13.2 years, undergoing posterior fusion and segmental instrumentation surgery for idiopathic adolescent scoliosis were studied for abnormalities of platelet count (PC), prothrombin time (PT) and partial thromboplastin time (PTT). Intraoperative and immediate postoperative values were obtained at 2, 4, 6, 12, 24, and 48 hours. All patients showed diminution of platelet counts during the study period, but mean values were reduced below normals only at 4 hours after operation. The PT was significantly elevated in all patients intraoperatively and for the first 24 hours postoperatively, with return to normal by 48 hours. The PTT levels were essentially unaffected at any time.

Adolescent

The epidemiology of prostate cancer part II: the risk factors.

The epidemiology of prostate cancer gives us some clues that its etiology is likely both environmental and genetic. There is extreme country to country variability in prostate cancer mortality. Countries in which dietary fat intake is greater have been shown to have higher prostate cancer mortality rates leaving some to conclude that dietary fat causes prostate cancer. Migration studies show that men moving from Japan and China adopt increased risks of prostate cancer. Second- and third-generation Japanese Americans and Chinese Americans actually have risks of prostate cancer similar to white American men. This is highly suggestive that prostate cancer has an environmental influence. The differences in black-white mortality and newer data suggesting a higher mortality among Jamaican and Brazilian men of African descent suggest there may be a genetic predisposition to prostate cancer. Some have suggested certain polymorphisms increase prostate cancer risk, whereas others are searching for genetic mutations that may increase prostate cancer risk. Africans may have an increased prevalence of these genetic risk factors. Ultimately, the cause of prostate cancer is likely to be a combination of environmental and genetic factors.

Age Factors

Cortical development: a role for spontaneous activity?

Patterned spontaneous activity seems important in the development of the retina and its projections, and it has now been shown that early retinal activity is faithfully transmitted through the thalamus. The modular organization of the visual cortex is also dependent on activity but not necessarily that originating in the retina.

Aging

Radical prostatectomy: is the perineal approach more difficult to learn?

PURPOSE: We assessed the relative difficulty with which radical perineal and retropubic prostatectomy operations are learned. MATERIALS AND METHODS: The first 10 radical perineal and retropubic prostatectomies performed by 6 graduating urology residents were reviewed for patient and tumor characteristics, duration of surgery and hospitalization, and complication rates. RESULTS: A total of 120 patients was reviewed. Mean hospital stay was 2.5 days less after radical perineal prostatectomy, and estimated blood loss, number of transfusions and complication rates were also less for this procedure. All parameters used to estimate the outcome of the procedure indicated that radical perineal prostatectomy was learned more quickly than radical retropubic prostatectomy. CONCLUSIONS: In a residency training program radical perineal prostatectomy was learned at least as easily as retropubic prostatectomy. Due to expanding indications for this procedure, these findings should encourage urological surgeons to develop their skill with this approach.

General Surgery

Correlating imaging and histopathology of an odontogenic keratocyst in the nevoid basal cell carcinoma syndrome.

We present the correlative diagnostic imaging and histological findings in a case of multiple odontogenic keratocysts (OKC) associated with the Nevoid Basal Cell Carcinoma Syndrome (NBCC). Whilst CT displayed aspects of bone morphology not visible on the plain films, contrast-enhanced MR provided the essential macropathological detail, including focal wall-enhancement and iso-intense intraluminal soft-tissue masses which correlated with the histological findings of focal inflammatory ulceration of the cyst lining, orthokeratosis and cell debris. The features identified by these combined imaging techniques are helpful in distinguishing the OKC from other cysts or neoplastic lesions and can therefore alter surgical management.

Basal Cell Nevus Syndrome

Alkaline encrusted cystitis associated with malakoplakia.

Alkaline encrusted cystitis is a rare inflammatory condition of the bladder which has been reported sporadically over the past 80 years. It is caused by infection with urea splitting organisms leading to the deposition of inorganic salts on to the surface of the bladder. We present three cases of alkaline encrusted cystitis. In two cases the encrusted area was associated with foci of malakoplakia. The third case occurred in a patient who had received chemotherapy for acute lymphoblastic leukaemia. To our knowledge, these are the first cases of malakoplakia associated with alkaline encrusted cystitis. These two conditions have a number of clinical and aetiological similarities, and may have more in common than has been previously thought.

Adolescent

Pneumonitis in a lupus twin pregnancy: a case report.

We describe a patient with systemic lupus erythematosus (SLE), whose pregnancy was complicated by fulminant lupus pneumonitis and pericarditis. Maternal disease responded to therapy and twin girls were delivered, both with thrombocytopenia, one of whom died of an intraventricular haemorrhage. Pneumonitis is a rare complication of lupus in pregnancy which may be fatal. We suggest patients with previous severe pneumonitis should have lung function tests at the onset of pregnancy, and treatment be modified to suppress flare if there is any indication of severe pneumonitis in early pregnancy.

Adult