Efficacy of oral ivermectin paste against mucosal stages of cyathostomes.
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Administration, Oral↗
Biomedical subjects
S Love
Publications and source records attributed to S Love.
Motor neuron disease with neurofibrillary tangles in a non-Guamanian patient.
Neurofibrillary tangles are described in Guamanian and post-encephalitic forms of motor neuron disease (MND) but not in sporadic MND. We report the neuropathological findings in a 79-year-old man who died after a 1-year history of MND without extrapyramidal features or dementia. There was no family history of neurological disease and he had not visited Guam. The spinal cord showed loss of anterior horn cells, and skeletal muscle typical changes of denervation. The brain appeared macroscopically normal but histology revealed many neurofibrillary tangles, particularly in medial temporal lobe structures, insula, nucleus basalis, hippocampus, oculomotor nucleus, raphe nuclei and locus ceruleus. Neurofibrillary tangles were not seen in the primary motor cortex, which appeared histologically unremarkable. Occasional tangles were present in the substantia nigra and pontine nuclei. None were seen in the cerebellum, medulla or spinal cord. The tangles were argyrophilic, and, in sections stained with thioflavin-S, both the intracellular and the extracellular tangles fluoresced strongly under ultraviolet light. The intracellular neurofibrillary tangles reacted strongly with an antibody to tau protein, and only occasional tangles showed weak ubiquitin immunoreactivity. Scattered neuropil threads were present in the cortex in the areas of neurofibrillary tangle formation. No plaques were present in any part of the brain and no A4/beta protein immunoreactivity was detected. Ultrastructural examination revealed Alzheimer-type neurofibrillary tangles composed of paired helical filaments. The present findings further extend the spectrum of diverse neurological disorders associated with neurofibrillary tangles.
Aged↗
Mitoxantrone and cytosine arabinoside as treatment for acute myeloblastic leukemia in older patients.
The majority of patients with acute myeloid leukemia (AML) are elderly, and their response to chemotherapy is poorer than that of younger patients. The combination of mitoxantrone (MTN) and cytosine arabinoside (Ara-C) is a possible alternative to an anthracycline/Ara-C combination for the treatment of AML in these patients. Of 52 older patients (> 59 years) referred over a 3.5-year period, 33 patients (age range 60-78 years, median 67 years) received MTN and Ara-C as therapy for newly diagnosed AML. MTN was administered at a dose of 12 mg/m2/day, intravenously, for 3 days (23 patients), or 10 mg/m2/day for 5 days (10 patients), and Ara-C at a dose of 100 mg/m2 twice daily, intravenously, for 7 days. Complete remission (CR) was achieved in 16/33 patients (48%). The median remission duration was 6 months (range 1-37 months). The median survival was 14 months for those who achieved CR compared with 9 months for those with resistant disease. Two patients remain in first CR after 13 and 37 months, but three patients died whilst receiving consolidation therapy. In selected elderly patients with AML, the combination of MTN and Ara-C provides an acceptable alternative to an anthracycline/Ara-C regimen, with a higher CR rate than historical controls. However, the CR rate and remission duration remain low compared with those of younger patients, supporting the need to investigate new approaches to treatment in this population.
Age Factors↗
Proliferating cell nuclear antigen (PCNA) immunostaining--a prognostic factor in ovarian cancer?
The measurement of tumour cell proliferation is becoming increasingly recognised in defining prognostic groups. Proliferating cell nuclear antigen (PCNA) immunolocalisation can be used as an index of cell proliferation and may define the extent of departure from normal growth control. The monoclonal antibody PC10 stains PCNA in archival paraffin-embedded tissue. This study investigates its potential as a prognostic marker in early and advanced ovarian cancer. A three-stage immunoperoxidase technique was developed to detect the monoclonal antibody PC10. Archival paraffin-embedded tissue from 19 stage I ovarian tumours (13 malignant and six borderline) and 79 advanced (stage IIb-IV) ovarian tumours (patients entered into the Third North-West Thames Ovarian Cancer Trial) was immunostained with PC10. PC10 immunostaining was performed successfully in 91.8% of cases. The PC10 labelling index (PC10 LI) ranged from 1.5% to 88% with a mean value of 47.4%. Stage I borderline tumours had significantly lower PCNA labelling indexes than stage I malignant tumours (P < 0.048). In advanced disease there was an inverse correlation between PC10 and overall survival, and in those patients who underwent good debulking surgery (37 patients with disease < 2 cm diameter) a low PC10 value (< 36.5%) correlated with improved survival (log-rank trend test for survival, chi 2 = 5.75, P = 0.017). PCNA immunostaining defines a good prognostic subgroup in adequately debulked patients with ovarian cancer.
Adult↗
Neurofibrillary tangles in Niemann-Pick disease type C.
Post-mortem neuropathological examination of five cases of Niemann-Pick disease type C revealed neurofibrillary tangles in many parts of the brain. Tangles were a consistent finding in the hippocampus, hypothalamus, substantia innominata, midbrain pons and medulla. Other regions of the brain in which tangles were present included neocortex, basal ganglia, thalamus, cerebellar cortex in one case, and dentate nucleus in another. The tangles were argyrophilic, fluoresced under ultraviolet light when stained with thioflavin S, and reacted strongly with antibody to tau protein. Some of the tangles could be immunostained for ubiquitin. Electron microscopy, performed in one of the cases, showed the tangles to consist of paired helical filaments ultrastructurally identical to those of Alzheimer's disease. The distribution of the tangles in the central nervous system as a whole and also within many individual neurons corresponded fairly closely with that of the abnormal storage material. Both the tangles and the storage material extended into, and distended, the proximal parts of many dendrites and axons. No A4/beta protein, either in the form of plaques or in the walls of blood vessels, was detected in any of the cases. Our findings suggest that neurofibrillary tangles are a common feature of Niemann-Pick disease type C and that their formation may be a reaction to the abnormal storage material.
Adolescent↗
Mantle cell lymphoma: natural history defined in a serially biopsied population over a 20-year period.
BACKGROUND: The histological, immunological and molecular characteristics of mantle cell lymphoma have only recently been delineated. Amongst these characteristics possible factors of prognostic significance include histological growth pattern and blastoid change. PATIENTS AND METHODS: 66 previously untreated cases of mantle cell lymphoma were identified in a retrospective analysis. In 50 cases serial biopsies had been taken during the disease and in 20 cases autopsies had been performed. Besides established factors of prognostic significance, histological growth pattern and blastoid change were examined. RESULTS: 32 patients achieved an initial complete remission or good partial remission with most cases relapsing or progressing within 2 years. The median survival was 36 months. Factors predicting a poor outcome were high presenting stage, age > 70, low sodium, low albumin and splenomegaly. Blastoid transformation was also a poor prognostic feature, occurring in 32% of cases during life and in 70% of autopsies. Histological growth pattern had no influence on outcome. CONCLUSION: This study emphasises the difficulties in treating mantle cell lymphoma and the high frequency and prognostic importance of histological transformation.
Aged↗
Epidemiological risk factors associated with a diagnosis of clinical cyathostomiasis in the horse.
Multiple logistic regression was used to assess epidemiological risk factors associated with the diagnosis of cyathostomiasis in 87 cases of chronic diarrhoea in the horse. Age, season and the period since last receiving anthelmintics were identified as important risk factors using chi-square and two-sample t test analyses, whereas access to grazing, shared grazing with other horses and recurrence of signs were only weakly associated with a diagnosis of cyathostomiasis. Multivariate analysis of the parameters using logistic regression was performed. The final model included age, season and time since last deworming. At a predicted probability of cyathostomiasis of 0.5, the model had a specificity of 86.0%, sensitivity of 66.7%, overall correct classification of 79.3%, a positive predictive value of 71.4% and a negative predictive value of 83.1%. The results of this study indicated that the specified variables and factors may be useful in the differentiation of clinical cyathostomiasis from other causes of chronic diarrhoea, based on case history alone.
Animals↗
Patterns of survival in patients with recurrent follicular lymphoma: a 20-year study from a single center.
PURPOSE: To examine outcome of treatment for patients with recurrent follicular lymphoma. PATIENTS AND METHODS: Two hundred twelve newly diagnosed follicular lymphoma patients were studied. One hundred seventy-nine were initially treated successfully. Recurrent or progressive lymphoma developed in 116. Treatment was given according to disease stage and current protocols, mostly with single alkylating agents. A policy of repeated lymph node and bone marrow biopsy was pursued. RESULTS: The overall median survival duration was 9 years, with a median follow-up duration of 12 years. Following recurrence, the median survival duration was 4 1/2 years. Only eight of 116 patients with recurrent disease died of causes unrelated to lymphoma. The overall response rate to first re-treatment was 78% and showed slight decline with successive recurrences, reaching 48% after the fourth treatment. The median duration of second remission was 13 months, (v 31 months for first remission), with the only significant predictive factor being quality of remission. Multivariate analysis showed only age at recurrence and number of prior treatments to correlate with survival after first recurrence. Survival after second remission was only correlated with age and quality of response: Kaplan-Meier estimates gave 53% of patients reaching second complete remission alive 10 years later, compared with 28% in partial remission. CONCLUSION: Age and previous and continuing responsiveness of follicular lymphoma to therapy are the principal determinants of survival following recurrence. Improvement in survival with new treatments will be demonstrated most readily in older patients, while more intensive approaches should be tested in younger patients in whom remission is achieved with difficulty.
Age Factors↗
Evidence that the agent of equine grass sickness may reach neurons by retrograde axonal transport.
Sera from acute and chronic cases of natural grass sickness or normal horses were injected into the parotid salivary gland of ponies. This gland receives its sympathetic innervation from the ipsilateral cranial cervical ganglion. None of the ponies showed any local or systemic signs of illness. After one week the cranial cervical ganglia, stellate and coeliaco-mesenteric ganglia were removed for histological study. Pathological changes were found only in the cranial cervical ganglion ipsilateral to a parotid salivary gland which had received an injection of grass sickness serum. Four out of five batches of test sera from cases of acute natural grass sickness were associated with chromatolytic changes in neurons; the remaining batch of serum produced no abnormalities. The most severe chromatolytic changes were induced by two samples obtained from horses whose signs of grass sickness had been present for less than 12 hours. A serum sample from a chronic case of grass sickness of three weeks duration did not produce chromatolysis but was associated with a moderately severe inflammatory infiltrate and neuronophagia in the ipsilateral cranial cervical ganglion. One batch of serum was size fractionated to separate components with molecular weights above or below 30 kDa. Only the fraction containing components above 30 kDa induced chromatolytic changes.
Acute Disease↗
Synthetic, structural and biological studies of the ubiquitin system: the total chemical synthesis of ubiquitin.
The small protein ubiquitin (76 amino acids) has been synthesized under optimized conditions by Merrifield solid-phase methodology using the N alpha-Fmoc protecting group. The crude polypeptide mixture was purified to homogeneity by gel filtration, dialysis and a combination of cation- and anion-exchange chromatography to yield ubiquitin. Amino acid analysis, enzymic digestion and sequencing by automated Edman degradation were used to authenticate the primary structure. Isoelectric focusing and m.s. were used to demonstrate that the final product was greater than 98% pure with a final yield of 93 mg (4.3%) from a single synthesis on a 0.25 nmol scale.
Amino Acid Sequence↗
Reduced levels of globular and asymmetric forms of acetylcholinesterase in rat left ventricle with pressure overload hypertrophy.
The aim of the present work was to determine the effect of abdominal aortic stenosis on molecular forms of acetylcholinesterase (AChE) in rat heart. Pressure-overload, left ventricular hypertrophy was produced in male Sprague-Dawley rats by suprarenal abdominal aortic constriction. After two weeks the relative heart weight was increased over 20% compared to sham-surgical controls, mostly due to left ventricular enlargement. Aortic constriction reduced AChE activity per wet weight and per unit protein by 25-30% in the left ventricle and interventricular septum, but not in the other chambers. However, total AChE activity per chamber was normal in the left ventricle and interventricular septum, but was elevated in the atria. The molecular forms of AChE were separated in linear sucrose gradients and their specific activities were calculated from the resulting percent activities and total AChE activities. This data showed that although aortic constriction had no effect on ratios of the various forms, it did reduce the specific activities of globular and asymmetric forms in the left ventricle and interventricular septum. The reduced AChE activity suggests that slower rates of ACh hydrolysis occur in the left ventricle in pressure-overload hypertrophy.
Acetylcholinesterase↗
Long-term results of a randomised trial of short-course low-dose adjuvant pre-operative radiotherapy for rectal cancer: reduction in local treatment failure.
A prospective randomised multicentre trial compared pre-operative radiotherapy followed by surgery with surgery alone for rectal cancer < or = 12 cm from the anal verge. Of 468 patients (mean age 67 years, range 31-94, 273 males) who met the entry criteria, 228 were randomised to radiotherapy (3 x 5 Gy over 5 days within 2 days of operation) followed by surgery, and 239 to surgery alone. Randomisation was unknown in 1 patient. Follow-up to death or 5 years was achieved in 454 (97%) patients. 31 (7%) of the 468 patients died within 30 days of operation (radiotherapy and surgery 21 [9%], surgery alone 10 [4%]; P < 0.05). Cardiovascular and thromboembolic complications were more common after radiotherapy and surgery (30, 13%) than after surgery alone (8, 3%; P < 0.005). Of the 280 patients who had curative surgery, 52% of those who had radiotherapy and surgery and 56% of those who had surgery alone survived 5 years (P = 0.88). 395 patients attended outpatients clinics at least once. Local treatment failure was identified during follow-up in 82 patients [31/185 (17%) radiotherapy and surgery; 51/210 (24%) surgery alone; P < 0.05]. It occurred in 33 of the 258 patients who had a curative resection and attended outpatients [radiotherapy and surgery, 11/120 (9%), surgery alone, 22/138 (16%); P = 0.08]. Long-term survival was unaffected, but long-term local recurrence was reduced by the addition of low-dose radiotherapy to surgery. Peri-operative mortality was, however, increased.
Adult↗
A 27 kDa heat shock protein that has anomalous prognostic powers in early and advanced breast cancer.
This paper describes a prospective immunohistochemical analysis of 27 kDa heat shock protein (HSP27) in 361 patients with primary breast cancer in relation to disease-free survival (DFS) and survival from first relapse (SR). Oestradiol (ER) and progesterone (PR) receptors were also quantitated and related to the HSP27 data. While ER positively predicted a good outcome for both DFS and SR, HSP27 positivity predicted a prolonged SR but short DFS. The association between HSP27 and DFS only attained statistical significance in node-negative patients. Subgroup analysis reinforced the complementary relationship of HSP27 and ER for SR and opposing influences for DFS. In both node-negative and node-positive women, ER+ HSP27- patients had a longer DFS than ER- HSP27+ counterparts. There was no relationship between HSP27 and overall survival. HSP27 staining was highly correlated with ER but not PR, patient age, tumour size or menstrual status. There was a marginal correlation (P = 0.04) with histological grade with well-differentiated tumours having the highest HSP27. Cox multivariate regression analysis of the contribution of HSP27 in the presence of data on ER, PR, stage, nodal status and histological grade indicated that HSP27 was not of independent prognostic importance for DFS or overall survival and was only of borderline significance for OS (P < 0.07). However, in the absence of ER and PR data, HSP27 staining is an effective way of getting the same prognostic information. HSP27 staining appears to correlate with different biological features in early and advanced breast, high HSP27 being linked with short DFS in node-negative patients but with prolonged survival from first recurrence.
Breast Neoplasms↗
Autopsy findings in two cases of neonatal herpes simplex virus infection: detection of virus by immunohistochemistry, in situ hybridization and the polymerase chain reaction.
We describe the pathological findings in two fatal cases of neonatal infection with herpes simplex virus. One had an encephalitis caused by herpes simplex virus type 2 (HSV-2); the other had a disseminated infection with herpes simplex virus type 1 (HSV-1). Confirmation of the diagnosis was obtained by use of the polymerase chain reaction to amplify viral DNA from paraffin sections of autopsy tissues. By using primers which amplify fragments of the HSV-1 thymidine kinase gene and HSV-2 glycoprotein gene respectively it was possible to discriminate between infection with HSV-1 and HSV-2. In contrast, immunohistochemistry and in situ hybridization using commercially available reagents did not distinguish between HSV-1 and HSV-2 infection. However, immunohistochemistry and in situ hybridization are probably more reliable than the polymerase chain reaction for assessment of the distribution of virus in different tissues.
Autopsy↗
Demonstration of mitochondrial ribosomal RNA in frozen and paraffin-embedded sections of skeletal muscle by in situ hybridization.
We have used in situ hybridization with synthetic oligonucleotide probes to the 16S sub-unit of mitochondrial ribosomal RNA to detect mitochondrial accumulations in biopsies of skeletal muscle from 16 patients with mitochondrial myopathies. In all cases, the distribution of the hybridization signal matched the pattern of succinate dehydrogenase activity in adjacent cryostat sections. In situ hybridization also allowed visualization of mitochondrial accumulations in paraffin-embedded sections of skeletal muscle that had been fixed in either De Castro's solution or formalin. DNase pre-treatment did not significantly diminish the intensity of hybridization signal, suggesting that the hybridization is predominantly to RNA. The advantages of this technique are that it allows the investigation of mitochondrial disorders when only paraffin-embedded tissue is available and should also facilitate the demonstration of mitochondrial accumulations in tissues other than skeletal muscle.
Biopsy↗
Absence of Epstein-Barr virus RNA in multiple sclerosis as assessed by in situ hybridisation.
Epidemiological and serological evidence has suggested a role for Epstein-Barr virus infection in the aetiology of multiple sclerosis. Epstein-Barr virus-specific RNA was looked for in the brains of 10 patients with multiple sclerosis by in situ hybridisation. A total of 21 plaques was examined. In all of these preservation of RNA was shown by hybridisation of control probes to mitochondrial rRNA but no signal was detected with the Epstein-Barr virus probes. It is unlikely that persistent or latent Epstein-Barr virus infection of the CNS occurs in multiple sclerosis, although present findings do not exclude a role for Epstein-Barr virus in the initiation of this disorder.
Aged↗
Beta-adrenergic receptors, adenylate cyclase activation, and myofibril enzyme activity in hypothyroid rats.
A previous study in intact animals assessed cardiovascular alterations in surgically thyroidectomized rats. Hemodynamic challenge via isoproterenol infusion identified abnormal left ventricular relaxation. Challenge by aortic occlusion revealed a latent deficiency in left ventricular contractility which was not apparent during beta-agonist challenge. The present study utilized left ventricular cardiac tissue obtained from the identical control and thyroidectomized animals from which intact heart hemodynamic information had been obtained. Biochemical systems were selected for evaluation based on demonstrated hemodynamic alterations, i.e., beta-adrenergic receptor number/function and contractile protein enzyme properties. The number of beta-receptors on hypothyroid cardiac membranes was significantly decreased, but receptor agonist affinity was not influenced. Basal adenylate cyclase activity in cardiac membranes from control and thyroidectomized rats was nearly identical; however, isoproterenol activation was diminished in hypothyroid cardiac membrane, particularly at the higher levels of beta-agonist stimulation. Adenylate cyclase enzyme activation by forskolin was not influenced by thyroidectomy; however, activation by sodium fluoride was reduced approximately 30% when compared with preparations from control rats. Cardiac myofibrillar enzyme activity for adenosinetriphosphatase (ATPase) was significantly lower in thyroidectomized rats. Despite reduced ATPase activity, myofibrillar calcium sensitivity was unaltered. Myofibrillar creatine kinase enzyme activity was not influenced by thyroidectomy; therefore, compartmentalized ATP regeneration potential via creatine kinase was enhanced relative to substrate utilization via ATPase. Thus hemodynamically significant cardiac influences of hypothyroidism are mediated, at least in part, via 1) reduced beta-receptor number, 2) diminished catecholamine-induced activation of adenylate cyclase, and 3) reduced myofibrillar ATPase activity.
Adenylyl Cyclases↗
Pathological findings associated with trigeminal neuralgia caused by vascular compression.
Vascular compression of the trigeminal nerve root accounts for more than 80% of intractable cases of trigeminal neuralgia, but the pathogenesis is still debated. The authors report the ultrastructural changes in the trigeminal nerve root of a patient with trigeminal neuralgia, at the point of compression by a large, medially placed petrosal vein, and compare these with the findings in six cases of trigeminal neuralgia not related to vascular compression. Vascular compression of the trigeminal nerve root was associated with focal loss of myelin and close apposition of the demyelinated axons with few intervening astrocytic processes. No inflammatory cells were present. Immunoelectron microscopy for glial fibrillary acid protein confirmed that astrocyte processes were largely confined to the periphery of the lesion. Of the other six rhizotomy specimens, only one, from a patient with multiple sclerosis, showed demyelination with intervening astrocyte processes, perivascular lymphocytes, and lipid-laden macrophages. These findings support the hypothesis that ephaptic transmission plays a role in the pathogenesis of trigeminal neuralgia related to vascular compression.
Adult↗