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Biomedical subjects

N M Smith

Publications and source records attributed to N M Smith.

At least 19 recordsLinked to original sources
PubMed2001

Lethal X-linked microcephaly with dysmorphic features, bilateral optic pathway aplasia and normal eyes.

We describe a family, consisting of two brothers and a maternal uncle who died of an apparently identical condition, within a few days of birth, suggestive of an X-linked mode of inheritance. The propositus (the older sibling) was investigated in detail and showed the following clinical features: microcephaly, facial dysmorphism, malformations of hands and feet, and cryptorchidism. Examination of the brain revealed arhinencephaly, a primitive gyral pattern, arrested cortical maturation, absence of corticofugal tracts and corpus callosum, agenesis of the optic pathway with preserved eyes and oculomotor system, absent auditory pathway, agenesis of the pars compacta of the substantia nigra and severe hypoplasia of the cerebellum and its connections. This family belongs to the group of X-linked microcephalies and has some features in common with the Juberg-Marsidi syndrome. The fact that the CNS abnormalities were incompatible with life and the facial dysmorphic features were quite different makes it unlikely that the affected individuals in this family had Juberg-Marsidi syndrome. However, this does not exclude the possibility that more restricted anterior induction defects may occur in some X-linked microcephalies such as Juberg-Marsidi syndrome resulting in prolonged survival.

Eye↗
PubMed2001

Protein solubility and folding monitored in vivo by structural complementation of a genetic marker protein.

Protein misfolding is the basis of a number of human diseases and presents an obstacle to the production of soluble recombinant proteins. We present a general method to assess the solubility and folding of proteins in vivo. The basis of this assay is structural complementation between the alpha- and omega- fragments of beta-galactosidase (beta-gal). Fusions of the alpha-fragment to the C terminus of target proteins with widely varying in vivo folding yield and/or solubility levels, including the Alzheimer's amyloid beta (A beta) peptide and a non-amyloidogenic mutant thereof, reveal an unambiguous correlation between beta-gal activity and the solubility/folding of the target. Thus, structural complementation provides a means of monitoring protein solubility/misfolding in vivo, and should find utility in the screening for compounds that influence the pathological consequences of these processes.

Amyloid beta-Peptides↗
PubMed2001

Prothrombotic megakaryocyte and platelet changes in hypertension are reversed following treatment: a pilot study.

Platelets are formed from, and their function determined by, bone marrow megakaryocytes (MK). Previous studies have found that hypertension is associated with accentuated platelet function and that some antihypertensive drug classes have antiplatelet activity. We measured MK ploidy (DNA content), size, granularity, and expression of the adhesion molecule glycoprotein (GP) IIIa, using flow cytometry and measures of platelet function, in 12 untreated hypertensive patients and 14 normotensive subjects. Eight hypertensive patients were then treated with losartan (50 mg daily), an angiotensin receptor antagonist that lowers blood pressure, and MK and platelet parameters re-measured after 6 weeks. Hypertensive patients had, as compared with matched normotensive subjects: increased MK ploidy (mean +/- SD) 22.9 +/- 2.2 N versus 20.8 +/- 1.6 N (2P = 0.009); increased platelet size, 10.67 +/- 1.03fl versus 9.26 +/- 0.72fl (2P < 0.001); increased platelet expression of GP IIIa, 108.6 +/- 22.5 versus 92.0 +/- 12.3 (2P = 0.036); and reduced platelet count, (207 +/- 52) x 10(9)/l versus (257 +/- 55) x 10(9)/l (2P = 0.026). Losartan significantly reduced MK ploidy, 22.6 +/- 2.2 N versus 21.4 +/- 1.9 N (2P = 0.006); MK size, 607 +/- 22 versus 579 +/- 16 (2P = 0.003); and lengthened cutaneous bleeding time, 424 +/- 86s versus 563 +/- 164s (2P = 0.011), in hypertensive patients. Losartan did not alter MK granularity or GP IIIa expression, or platelet count, size, mass, GP IIIa expression, or aggregation. The data suggest that platelet changes in hypertension may be secondary to changes in MKs, and that anti-hypertensive treatment can alter MKs and the function of platelets they produce. Since antihypertensive therapy reduces the risk of stroke and myocardial infarction, MKs are a novel therapeutic target for the prevention of vascular events.

Adult↗
PubMed2000

Broadsheet number 56: Mechanisms of fetal loss.

The most significant task of the pathologist examining a fetal death is, if possible, the provision of an explanation for the event, which will allow the clinical attendants to counsel the family in an informed and relevant manner. In some cases, no adequate explanation will be possible, though many conditions will be excluded and the importance of this exercise is worth emphasising. Often, however, a combination of fetal, maternal or placental conditions can be found and a full or partial explanation offered, and it is the purpose of this broadsheet to highlight some of these conditions and provide suggestions as to sources of further practical help.

Adult↗
PubMed2000

Unexpected childhood death due to hemolytic uremic syndrome.

Two cases of unexpected childhood death due to hemolytic uremic syndrome are reported. A 21-month-old girl who was discovered dead in bed following a short illness was found at autopsy to have overwhelming sepsis resulting from transmural colitis. Escherichia coli serotype 0157A was isolated from the intestine, and renal changes of hemolytic uremic syndrome were found. A 4-year-old girl died suddenly in hospital from intracranial hemorrhage while being treated for hemolytic uremic syndrome-related renal failure. Culture of urine and feces grew verocytotoxin producing E. coli. These cases demonstrate that hemolytic uremic syndrome may be a rare cause of unexpected childhood death and that the diagnosis may not be established prior to autopsy. Postmortem culture of tissues and fluids in cases of suspected sepsis in children may be essential in establishing this diagnosis, because histologic evaluation may be compromised by profound sepsis and tissue putrefaction. Accuracy in diagnosis may have significant public health and medicolegal consequences.

Autopsy↗
PubMed1999

Bilateral Wilms' tumor: a clinicopathologic review.

Bilateral Wilms' tumor occurs at a younger age than unilateral disease. While it generally has a good prognosis, it presents a therapeutic dilemma to balance curative surgical resection with preservation of renal tissue. A 15 year review of bilateral Wilms' tumors diagnosed at Princess Margaret Hospital was undertaken. Of 46 Wilms' tumor cases, eight were designated bilateral by diagnostic imaging (median age 1.1 years compared with 3.5 years for unilateral tumors). The surgical management entailed primary nephrectomy with contralateral biopsy in two patients, and bilateral biopsy and delayed resection in all remaining surviving patients (one patient died of perioperative complications). Seven patients had localized disease (stage I/II) and the six surviving patients received chemotherapy with vincristine and actinomycin; no patient received radiotherapy. All are alive and well (median follow-up 5.1 years). The remaining patient presented with pulmonary metastases and died of disease progression. Pathologic review revealed that four patients had truly bilateral disease demonstrable by histology, three had unilateral Wilms' tumor with contralateral nephrogenic rests, and in one patient the biopsies of the contralateral kidney showed neither tumor nor nephrogenic rests. In most cases pathological material was subject to external review. Follow-up demonstrates excellent renal function with compensatory hypertrophy in the remaining renal tissue. Conservative surgery and simple out-patient based, low toxicity chemotherapy is curative in most patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Platelets and stroke.

Platelets are anucleate cells with little or no capacity for de novo protein synthesis. Their potential haemostatic reactivity is established at or before thrombopoiesis by their precursor cell, the bone marrow megakaryocyte. In some pathologic conditions, the megakaryocyte-platelet-haemostatic axis (MPHA) becomes perturbed, resulting in the formation of hyperfunctional platelets which may contribute to the development of vascular disease or an acute thrombotic event such as ischaemic stroke or myocardial infarction. Laboratory measurements of platelet function have established that platelet reactivity is accentuated in acute ischaemic stroke, particularly following cortical rather than lacunar infarction. Whether accentuated platelet function is a cause or a consequence of stroke is not yet clear, but it is likely that patients with certain risk factor profiles have some degree of platelet activation preceding the stroke. Further work into the MPHA is required to establish whether enhanced post-stroke platelet reactivity can be referred to the megakaryocyte. The antiplatelet agents tested to date are effective in secondary but not primary prevention of stroke. This probably reflects the diverse pathophysiology of stroke: accentuated platelet function is only likely to be a significant factor in cortical stroke.

Animals↗
PubMed1998

Atypical mycobacterial lymphadenitis in childhood--a clinicopathological study of 17 cases.

AIMS: To assess the clinical and pathological features of atypical mycobacterial lymphadenitis in childhood to define the salient clinical and histological features. METHODS: 17 cases were included on the basis of positive culture or demonstration of bacilli of appropriate morphology and staining characteristics. RESULTS: The mean age at diagnosis was 4.86 years. All children were systemically well, with clear chest x rays. Unilateral cervical lymphadenopathy was the commonest mode of presentation. Differential Mantoux testing played no part in diagnosis. Clinical diagnosis improved with awareness. Treatment varied with surgeons opting for excision and paediatricians adding six months antituberculous chemotherapy. Acid- and alcohol-fast bacilli were identified in nine cases. Bacterial cultures were conducted in 16 cases and were positive for atypical or nontuberculous mycobacteria in 14, the main organism being M avium-intracellulare complex (11 cases). Histologically, 12 cases had bright eosinophilic serpiginous necrosis with nuclear debris scattered throughout the necrotic foci. Langhans type giant cells featured in the majority of cases but infiltration by plasma cells and neutrophils was not consistent. CONCLUSIONS: Atypical mycobacterial lymphadenitis of childhood represents a rare but significant disease with characteristic clinical and histological features.

Child↗
PubMed1997

Pattern of malformations in the axial skeleton in human triploid fetuses.

We examined the axial skeleton in 15 human triploid fetuses (10 with XXX and 5 with XXY sex chromosomes). All fetuses 14-29 weeks of gestational age (GA), underwent whole-body radiography, permitting analysis of the nasal bone and the spine. From 9 of these, detailed radiographs were taken of midsagittal blocks of the cranial base and the spine, permitting detailed analysis of the cranial base. NASAL BONE: Of 14 fetuses, where the nasal bone was seen on lateral projection, it appeared short in 10 cases. SPINE: The spine was normal in 7 of 15 fetuses; malformations occurred in 8. These were osseous fusions between 2 or more vertebral bodies, most frequently in the cervical and thoracic regions, and disproportions in the sizes of the cervical bodies. Fusions occurred in 5 cases alone, and in one case in combination with disproportions of vertebral size. Disproportions alone occurred in 2 cases. CRANIAL BASE: Malformation of the basilar part of the occipital bone was found in 5 of the 9 fetuses investigated. Of 9 fetuses, bilateral ossification centers of the postsphenoid bone occurred in 7, and shell-like ossification centers in 2. There was no difference in the type of malformations in the different axial fields related to genotype (XXX and XXY). CONCLUSION: The most remarkable findings in the axial skeleton of triploid fetuses are vertebral fusions in 6 of 15 cases; clefts of vertebral bodies, previously reported as common findings in trisomy fetuses, are not demonstrated.

Abnormalities, Multiple↗
PubMed1997

Mosaic partial trisomy 17 due to a ring chromosome identified by fluorescence in situ hybridisation.

We report on a 3-year-old-girl with mosaic partial trisomy 17 due to an additional ring chromosome 17 in 13% of cells analysed. This was identified by fluorescence in situ hybridisation (FISH) using a whole chromosome 17 specific paint as well as probes specific for the Smith-Magenis and Miller-Dieker regions of chromosome 17p. This girl showed mild developmental delay with subtle facial and other minor abnormalities including single palmar creases, generalised joint laxity, and a scoliosis.

Charcot-Marie-Tooth Disease↗
PubMed1997

A monoclonal antibody pool for routine immunohistochemical detection of human respiratory syncytial virus antigens in formalin-fixed, paraffin-embedded tissue.

Four monoclonal antibodies (MAbs) with specificities for epitopes on human respiratory syncytial virus (RSV) proteins preserved after formalin fixation and paraffin embedding were identified in fixed and embedded virus-infected HEp-2 cell pellets. The MAbs bound epitopes on the fusion protein, the nucleoprotein, the phosphoprotein, and the M2 protein of the virus. Following high-temperature antigen unmasking, immunohistochemical staining revealed RSV antigens in the lungs of five of seven children who died with confirmed RSV infection and in none of nine children who died for other reasons, with no evidence of RSV infection. Staining was cytoplasmic, granular, and confined to epithelial cells. Intense staining was seen at the apex of ciliated bronchial and bronchiolar epithelial cells in all five positive cases. In one case, of pneumonitis, infected pneumocytes were present in the alveoli and in several cases, CD68-positive, cytokeratin-negative alveolar macrophages stained for viral antigens. These antibodies may prove useful in studies of the pathogenesis of RSV infection.

Antibodies, Monoclonal↗
PubMed1997

Three-year follow-up of bibliotherapy for depression.

This study examined the durability of cognitive bibliotherapy for mild to moderately depressed adults by conducting a 3-year follow-up of participants from a previous study (C. Jamison & F. Scogin, 1995). The Hamilton Rating Scale for Depression, Beck Depression Inventory, and questions relating to participants' perceptions of the program were administered. Results indicated that treatment gains were maintained over the 3-year follow-up period and support the usefulness of cognitive bibliotherapy as an adjunct to traditional treatment modalities in a general adult population.

Adult↗
PubMed1997

Neurogenic chronic idiopathic intestinal pseudo-obstruction, patent ductus arteriosus, and thrombocytopenia segregating as an X linked recessive disorder.

We present a family with three affected males in two generations with congenital neurogenic chronic idiopathic intestinal pseudo-obstruction (CIIP), patent ductus arteriosus, and large platelet thrombocytopenia apparently segregating as an X linked recessive disorder. The pattern of segregation of DNA markers within the family is consistent with linkage to the previously described neurogenic CIIP (CIIPX) locus at Xq28. This combination may represent a new contiguous gene disorder and appears to have a good prognosis with supportive therapy.

Abnormalities, Multiple↗
PubMed1996

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Health Care Reform↗
PubMed1996

Ante-natal testicular torsion: only one cause of the testicular regression syndrome?

It has been suggested that the most likely cause of the Testicular Regression Syndrome (TRS) is ante-natal torsion of the testis. As testicular torsion is twice as common on the left this theory cannot explain the incidence of right sided or bilateral cases. From a 5-year retrospective surgical and pathological review, we confirmed that the left testis was the most commonly affected, that boys with TRS tended to be delivered closer to term, and that frequently both testes were present at birth, but one or both subsequently vanished. We also found that direct trauma can produce histological findings indistinguishable from TRS. Close to term, fetal testes are liable to be intrascrotal and therefore susceptible to direct trauma. As the left testis descends into the scrotum at an earlier stage than the right, it is therefore at greater risk of injury. Since the findings of TRS can be produced by direct trauma, we suggest that intra-partum trauma may predispose to the TRS.

Child, Preschool↗