Following historical "tracks" of hair follicle miniaturisation in patterned hair loss: Are elastin bodies the forgotten aetiology?

Pattern hair loss (PHL) is a chronic regressive condition of the scalp, where follicular miniaturisation and decreased scalp hair coverage occurs in affected areas. In all PHL cases, there is a measurable progressive shortening of the terminal hair growth duration, along with reduced linear growth rates. In both genders, PHL initially shows an increase in short telogen hairs ≤30 mm in length, reflecting a cycle completion of under 6 months in affected terminal hair follicles. To understand the miniaturisation process, we re-examine the dynamics of miniaturisation and ask the question, "why do miniaturised hair follicles resist treatment?" In the light of recent developments in relation to hair regeneration, we looked back in the older literature for helpful clues "lost to time" and reprise a 1978 Hermann Pinkus observation of an array of elastin deposits beneath the dermal papilla following subsequent anagen/telogen transitions in male balding, originally described by Arao and Perkins who concluded that these changes provide a "morphologic marker of the entire biologic process in the balding scalp." Thus, we have reviewed the role of the elastin-like bodies in hair pathology and we propose that alterations in elastin architecture may contribute to the failure of vellus-like hair reverting back to their terminal status and may indicate a new area for therapeutic intervention.

Gender differences in scalp hair growth rates are maintained but reduced in pattern hair loss compared to controls.

BACKGROUND: Hair loss is related to follicular density, programmed regrowth and hair productivity. OBJECTIVE: The dissatisfaction with hair growth in patients experiencing hair loss might be due to slower linear hair growth rate (LHGR). METHODS: LHGR and hair diameter was evaluated in Caucasian controls and patients with patterned hair loss employing the validated non-invasive, contrast-enhanced-phototrichogram with exogen collection. RESULTS: We evaluated 59,765 anagen hairs (controls 24,609, patients 35,156) and found thinner hairs grew slower than thicker hairs. LHGR in normal women was generally higher than in normal men. LHGR correlates with hair diameter (P < 0.006) and global thinning is associated with slower growth rates. Compared with hair of equal thickness in controls, subjects affected with patterned hair loss showed reduced hair growth rates, an observation found in both male and female patients. Males with pattern hair loss showed further reduction in growth rates as clinical severity worsened. However, sample size limitations prevented statistical evaluation of LHGR in severely affected females. LIMITATIONS: Caucasian ethnicity. CONCLUSION: In pattern hair loss, LHGR significantly contributes to the apparent decrease in hair volume in affected areas. In early onset, LHRG might have a prognostic value in females but not in males.

Development and operation of the defence COVID-19 lab as a SARS-CoV-2 diagnostic screening capability for UK military personnel.

BACKGROUND: In the face of the COVID-19 pandemic, the Defence Science and Technology Laboratory (Dstl) and Defence Pathology combined to form the Defence Clinical Lab (DCL), an accredited (ISO/IEC 17025:2017) high-throughput SARS-CoV-2 PCR screening capability for military personnel. LABORATORY STRUCTURE AND RESOURCE: The DCL was modular in organisation, with laboratory modules and supporting functions combining to provide the accredited SARS-CoV-2 (envelope (E)-gene) PCR assay. The DCL was resourced by Dstl scientists and military clinicians and biomedical scientists. LABORATORY RESULTS: Over 12 months of operation, the DCL was open on 289 days and tested over 72 000 samples. Six hundred military SARS-CoV-2-positive results were reported with a median E-gene quantitation cycle (Cq) value of 30.44. The lowest Cq value for a positive result observed was 11.20. Only 64 samples (0.09%) were voided due to assay inhibition after processing started. CONCLUSIONS: Through a sustained effort and despite various operational issues, the collaboration between Dstl scientific expertise and Defence Pathology clinical expertise provided the UK military with an accredited high-throughput SARS-CoV-2 PCR test capability at the height of the COVID-19 pandemic. The DCL helped facilitate military training and operational deployments contributing to the maintenance of UK military capability. In offering a bespoke capability, including features such as testing samples in unit batches and oversight by military consultant microbiologists, the DCL provided additional benefits to the UK Ministry of Defence that were potentially not available from other SARS-CoV-2 PCR laboratories. The links between Dstl and Defence Pathology have also been strengthened, benefitting future research activities and operational responses.

Diaphragmatic pathology: a cause of clinically unexplained death in the perinatal/paediatric age group.

Sudden unexpected death in infancy and childhood requires a 'full' post-mortem investigation. Guidance from the Royal College of Pathologists recommends sampling of all the major organs. However, the diaphragm does not feature in this or in most lists of routine histology. Our aim is to emphasize the importance of sampling the diaphragm for histological examination during autopsy. We describe three autopsy cases of clinically unexplained death in the perinatal and paediatric age group that showed significant pathology of the diaphragm. In Case 1, a previously healthy five-year-old girl collapsed suddenly and died four days later. In Case 2, an eight-month-old infant had repeated episodes of respiratory arrest that culminated in death. Autopsy demonstrated a predominantly diaphragmatic myositis. In Case 3 a female neonate had a respiratory arrest three days after birth and died less than a month later. Autopsy showed multiple large calcified necrotic fibres in the diaphragm. The diaphragm is seldom sampled at autopsy. In the first two cases a predominantly diaphragmatic myositis was either the direct or underlying cause of death. In the third case long-standing diaphragmatic pathology of uncertain cause may have contributed to the original respiratory arrest. Had the diaphragm not been examined histologically, the cause of death would have remained unascertained in these cases. In cases of sudden death in infancy and childhood, failure to reach a diagnosis may lead to undue suspicion falling upon the child's carers. This underscores the need for full histology at post-mortem in child deaths, including diaphragmatic sampling.

Effects of retinal image stabilization in acquired nystagmus due to neurologic disease.

We studied the effects of variable amounts of artificial retinal image stabilization (RIS) upon oscillopsia and visual acuity in eight patients with acquired nystagmus due to neurologic disease. We measured horizontal and vertical eye movements with the magnetic search coil technique and used these electronic signals to control the position of a visual stimulus on a screen in front of the patient. We also used an optical device to stabilize images of the real world upon the retina. During electronic stabilization, RIS was progressively increased until oscillopsia was abolished; this was achieved in all eight patients and corresponded to retinal image drift of 5 degrees/sec or less. In five patients with downbeat nystagmus, further increases in RIS caused the oscillopsia to reappear, but in the opposite direction. Electronic stabilization also improved visual acuity in four of five patients; the limitation of improvement could be related to coexistent visual system defects. Using electronic feedback, we could measure the range of RIS that any individual required to abolish oscillopsia; from this measurement, the components of the optical device that were best suited to provide a stable field of vision could be calculated.

Immunohistochemical localization of parathyroid hormone-related protein (PTHrP) in human term placenta and membranes.

Parathyroid hormone-related protein (PTHrP), the major factor responsible for hypercalcaemia of malignancy, is widely expressed in normal adult and fetal tissues. In this study, the distribution of PTHrP was examined in human term placenta and membranes by immunohistochemistry using antisera to PTHrP 1-34 and 37-67. PTHrP was detected in cuboidal epithelial cells of amnion and in cytotrophoblastic cells of chorionic laeve and adherent maternal decidua. In placenta, PTHrP 1-34 was detected in the syncytiotrophoblast, while PTHrP 37-67 activity was mainly present in the brush border of the syncytiotrophoblast. This study also identified PTHrP 37-67 associated with fetal vessels of placental villi. These findings may reflect the cellular distribution of intact PTHrP or sub-fragments derived by post-translational processing. Postulated actions of PTHrP in the uteroplacental unit include transport of calcium across the placenta, stretch of membranes, inhibition of uterine contractility, growth and differentiation, and vasoregulation.

Spongy degeneration of the white matter of the central nervous system associated with hyperglycinuria.

Five infants from two families with the clinical features of hyperglycinaemia and hyperglycinuria are described. In four of these cases spongy degeneration of the central nervous system is associated with lipid-filled glial cells and retarded myelination. The origin of these changes is discussed and the relationship of the lesions to the metabolic defect is reviewed. The importance of such cases in the understanding of the normal metabolism of the nervous system is stressed.

Examination of products of conception from previable human pregnancies.

The incidence, aetiology, and mechanisms of spontaneous abortion are outlined. A simplified classification of products of conception specifically orientated for routine histopathological laboratories rather than research centres is presented. Its introduction should not in itself greatly increase the work load of a service laboratory already examining such material. Specific practical problems are discussed and these are related to the clinical situation. The importance is emphasised of proper examination of tissues from pregnancies aborting after diagnostic amniocentesis, as well as those from therapeutic terminations performed for fetal abnormality or disease. Special techniques are suggested for processing suspected procured abortions. Finally the value is stressed of routine examination of spontaneously aborted material in the current and future management of the patient, in the furtherance of our knowledge of fetal diseases and of some of the major contributory factors to perinatal morbidity and mortality.

The maternal autopsy.

Careful study of reports prepared for the Confidential Enquiries into Maternal Deaths in England and Wales has made it clear that many maternal autopsy reports are not as informative as they might be. This is, in part at least, because no pathologist who does not work in a maternity unit can expect to see more than a handful of such deaths in a working lifetime. This paper describes briefly the particular features to look for at autopsy, stresses the importance of taking adequate material for histology and discusses some of the more significant histological findings, both of conditions which cause death and of those commonly associated with it.

Studies of influenza virus infection in newborn ferrets.

Influenza virus infection by the intranasal route was found to be invariably fatal in newborn ferrets. Some obviously died of influenza pneumonia; others died of aspiration pneumonia or showed only minimal or non-specific changes in the lungs. All, however, had severe lesions in the upper respiratory tract, and it is suggested that obstruction of airways and oesophageal passages, in combination with feeding difficulties, played a major role in causing death. The relevance of the findings to the pathology of cot deaths in human infants is briefly discussed.

Placental malaria and foetoplacental function: low plasma oestradiols associated with malarial pigmentation of the placenta.

Placental biopsies were taken immediately post partum from 65 Gambian mothers who had not received anti-malaria chemoprophylaxis during pregnancy whilst living in an area hyperendemic for Plasmodium falciparum malaria. The biopsies were examined without knowledge of the mothers' health or the outcome of pregnancies. Histologically, they were divided into two groups: those with macrophages containing malarial pigment in the inter-villous spaces, and those without such pathology. Babies with pigmented placentae had a mean (SD) weight for gestational age of 83.3 (10.6)%, which was significantly lower (p less than 0.01) than that of 91.2 (7.7)% in the non-pigmented group. The plasma oestradiol concentrations in the mothers who later delivered pigmented placentae were significantly lower from 32 weeks of gestation onwards, and did not continue to rise in the last trimester as they did in the non-pigmented group. The last trimester appears to be the critical time for protection of the foeto-placental unit against malaria. Anti-malaria chemoprophylaxis should be given to all pregnant women.

Frontal horn thin walled cysts in preterm neonates are benign.

BACKGROUND: Screening cranial ultrasound led to the discovery of isolated frontal horn cysts quite distinct from periventricular leucomalacia cysts. AIM: To clarify their significance, incidence, characteristics, causal factors or aetiology, and effect on long term outcome. DESIGN: A retrospective observational study of all first cranial ultrasound scans (total of 2914) performed during the period 1984-1994 inclusive found 21 neonates with smooth thin walled frontal horn cysts: 18 of 2629 scanned were of birth weight < 1500 g or gestation < 33 weeks, and three of 285 were > 33 weeks gestation. Sequential ultrasound, maternal records, and neonatal events were retrospectively assessed. In survivors, routine neurodevelopmental evaluations were obtained. Postmortem studies of one cyst were performed to determine the nature and origin of these lesions. RESULTS: Of the 21 subjects, 15 had isolated frontal horn cysts and six had additional ultrasound scan abnormalities, including four with subependymal haemorrhage. The sonographic features of frontal horn cysts were of distinctive morphology (elliptical, smooth, thin walled, ranging in size from 3 to 20 mm) and position (adjacent to the tip of the anterior horns). The cysts enlarged and then regressed by a median corrected age of 2 months. Subjects of < 33 weeks gestation (n = 18) had a median birth weight of 1465 g (range 720-1990) and median gestation of 30 weeks (range 24-32). There was no consistent perinatal course. The neurodevelopmental outcome in 10 of the 11 survivors with isolated frontal horn cysts was normal. Five subjects died from causes unrelated to brain pathology in the neonatal period, and one subject died after infancy. Histological examination of a cyst at autopsy in one additional subject subsequent to the period of study confirmed the cyst to be lined by neuroblasts and ependymal cells. CONCLUSIONS: The incidence of frontal horn cysts in this low birthweight population was 7 per 1000 (0.7%) subjects scanned. They are present in the first week of life, enlarge, and resolve spontaneously. Survivors with isolated frontal horn cysts appear to have normal neurodevelopmental outcome. The prognosis of these distinct frontal horn cysts therefore appears to be benign.

Management of hair loss in women.

Hair loss in otherwise healthy women presents several challenges for the clinician. The first is to identify the cause, which may be complicated by two or more secondary factors; the second is to find effective treatments; and the third is to establish requirements for long-term management. An optimal hair growth potential is considered to exist when specific parameters for biochemical variables are operating. These include red blood cell and serum folate concentrations within the normal range, serum vitamin B12 levels between 300 and 1000 ng/L, hemoglobin levels greater than 13.0 g/dL, and serum ferritin concentrations of 70 ng/mL or greater. The two predominant disturbances, diffuse androgen-dependent alopecia and chronic telogen effluvium, both require months of treatment before the benefits can be seen. During this time several follow-up investigations and reassuring consultations must occur. Current systemic antiandrogen regimens are highly effective, but the prospect of long-term therapy, possibly for life, is daunting. For some patients there is no systemic choice and topical treatment is the only option. Minoxidil is the only topical preparation currently licensed, but with no quantitative long-term data available, assessing its value in the long-term treatment of androgen-dependent alopecia is difficult.

"Medullary ray glomerular counting" as a method of assessment of human nephrogenesis.

Renal weight (left-right combined), as a parameter of renal development, is required to be less than half the normal value for age for a statistically confident diagnosis of hypoplasia. "Medullary ray glomerular counting" (MRGC), counting cortical glomerular generations, has been proposed as a simple technique of possibly greater sensitivity. Recent development of the Disector method for the unbiased stereological estimation of total glomerular number has provided a, hitherto unavailable, "golden standard" with which to determine the diagnostic potential of MRCG. Both "true" (actual number of generations seen) and "assumed" (a subjective "guess" of the total number of generations) MRGC counts were determined in 11 pairs of kidneys from spontaneously aborted, normally developed, non-malformed fetuses (gestational age: 15-40 weeks). Each kidney was randomly analysed blind and on two separate occasions by two paediatric pathologists using a written protocol. Results were compared with unbiased stereological estimates of glomerular number. Intra- and inter-observer and intra- and inter-(left-right)renal reproducibility were analysed. In conclusion, MRGC, using "real" counts, is a highly reproducible parameter of renal development from 15-36 weeks' gestation. Sensitivity for detection of both hypoplasia and maturation delay increase with gestational age and generally exceeds that of renal weight.