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Biomedical subjects

H Ramsay

Publications and source records attributed to H Ramsay.

At least 19 recordsLinked to original sources

Socio-demographic and clinical characteristics of Jamaican adolescents with HIV/AIDS.

BACKGROUND: Clinical symptomatology and socio-demographic factors have not been characterized in Jamaican adolescents with HIV/AIDS. METHODS: We studied these factors in 25 HIV-positive Jamaican adolescents, 10-19 years of age, who were seen at the Centre for HIV/AIDS Research, Education, and Services (CHARES) between the years 1996 and 2002. Data were collected between June 2003 and August 2003 from CHARES social work files and The University Hospital of the West Indies (UHWI) medical records. Microsoft Excel was used to compile descriptive statistics for the data. RESULTS: The mean age of HIV diagnosis was 15.6 (+/-3.09) years, and the mean age of enrollment at CHARES was 16.3 (+/- 2.9) years. Consensual sexual intercourse was the most prominent mode of transmission (56%), followed by vertical transmission (16%), unknown (16%), forced sexual intercourse (8%), and blood transfusion (4%). The predominant clinical presentations among these adolescent patients were generalized dermatitis (77.2%) and lymphadenopathy (50%). Of the patients for whom clinical status could be determined, 70% were "Severely Symptomatic ". Of these patients only 14% were recommended for antiretroviral treatment. CONCLUSIONS: These findings reinforce the need to globally incorporate the goal of the 2002 Joint United Nations Programme on HIV/AIDS (UNAIDS) "to provide reproductive health services, including low-cost or free condoms, voluntary counselling and testing, diagnosis and treatment of sexually transmitted diseases and infections for adolescents in order to effectively prevent HIV infection " (1).

Acquired Immunodeficiency Syndrome↗

Apoptosis and regression of embryonic mesenchyme in the development of the middle ear spaces.

Apoptosis was studied using temporal bones from three fetuses representing different times of gestation and from three neonates. Paraffin-embedded sections 20-microm thick were studied using the terminal deoxynucleotide transferase-mediated dUTP nick-end labeling method based on 3'-end-labeling of fragmented DNA. Phenotyping of the immune cells was performed using regular monoclonal antibodies. In the bone marrow the granulocyte series dominated and the number of cells in the macrophage series was noticeably fewer, with apoptotic cells occurring in both. In the embryonic mesenchyme, solitary apoptotic cells occurred in all locations in both the fetuses and neonates. Apoptosis is a basic factor in the regression of embryonal mesenchyme, but may not be preprogrammed. Basic scientific data obtained from modified tissue cultures show that mechanical forces cause cells to switch between different genetic programs. It is suggested that the act of swallowing causes periodic changes in the amniotic fluid pressure and provides the necessary force for regression of the mesenchyme by apoptosis.

Apoptosis↗

Aeration and drainage pathways of Prussak's space.

OBJECTIVE: the purpose of this study was to document the aeration and drainage pathways of Prussak's space. METHODS: 55 temporal bones with an age range from neonate to 11 years of age were serially sectioned to 20 microns, every 10th section was saved and stained by Hematoxylin eosin. Each consecutive section was studied as to the connections of Prussak's space to adjacent compartments and measurements of the dimensions were made for both Prussak's space and its aeration pathways. RESULTS: the classic aeration pathway via the posterior pouch, as described by Prussak in 1867, was found in 34 ears (62%). In 19 (36%), aeration occurred superior to the posterior pouch in the region of the lower lateral attic and the upper mesotympanum. In these ears the posterior pouch had formed, but its superior limit ended blindly in the tympanic membrane. In two temporal bones the aeration pathway was from the anterior pouch and in these cases also a blind posterior pouch had developed. In one temporal bone an auxiliary pathway in addition to the route via the posterior pouch was through the roof (the lateral malleal ligamental fold) of Prussak's space to the overlying lateral malleal space. The height of the posterior pouch varied with a range from 0.5 to 2.4 mm, and the greatest width, which was towards the posterior tympanic spine, varied from 1.6 to 3.2 mm. The superiorly blind posterior pouch was shorter, ranging from 0.4 to 1.2 mm in height. The most frequent route of the chorda tympani nerve was running from 0.5 to 1 mm medial to the posterior malleal ligament in the anterior half of the pouch, joining it posteriorly, or it was connected to it by a short fold, 37 ears (67%). In 18 cases (33%) the chorda was surrounded by its own fold, thus entirely separate from the posterior malleal ligamental fold during its entire course across the tympanum. CONCLUSIONS: we have made a detailed documentation of the aeration and drainage pathways of Prussak's space and the findings concur, with important modifications, with Prussak's original description. There is no evidence for contemporary claims that Prussak's space would be aerated superiorly between the lateral incudal and malleal folds. Prussak's space and its aeration pathway is an unit of its own, entirely separate of the major epitympanic compartments which are aerated via the tympanic isthmus. Due to frequent disease processes in the lower lateral attic and posterior mesotympanum, Prussak's space and its aeration pathway are likely to become blocked. This may lead to obliteration of Prussak's space and to the development of retraction pocket or papillary ingrowth cholesteatoma.

Child↗

Spread and fate of amniotic fluid cellular content in the middle ear.

In this study, 24 temporal bones with an age range from neonates to 23-month-old infants were serially sectioned and studied for the spread and fate of amniotic fluid cellular content (AFCC) in the middle ear and mastoid. Most children had had either a moderate or massive contamination. AFCC clusters were found to spread to all compartments, with the sites of predilection being the stapes region, the lower lateral attic and the tympanic isthmus. AFCC created an intensive foreign body giant cell reaction and the foreign material practically dissolved in 5 months as a result of the organization process. Tiny remnants of AFCC appeared as late as 15 months after birth. It seems likely that AFCC contamination predisposes the ears to recurring otitis media. The sequalae of the massive granulation tissue development involves obliteration of Prussak's space and its aeration routes, as well as blockage of the tympanic isthmus, leading to extensive disease in the major attic compartments.

Age Factors↗

Foreign body neonatal otitis media in infants.

HYPOTHESIS: An influx of amniotic fluid cellular content (AFCC) into the middle ears during birth may lead to the development of a chronic inflammatory process in the form of varying amounts of granulation tissue even if signs of otitis media are absent. This foreign body neonatal otitis media may predispose the child to recurrent otitis media. BACKGROUND: Foreign body neonatal otitis media caused by AFCC was described by Aschoff and elaborated by Wittmaack 100 years ago. Recent studies have shown how AFCC spreads to various middle ear compartments and causes histologic changes, the severity of which is related to the amount of AFCC. Specific elements become phagocytized after the first months of life but have caused the formation of inflammatory polyps and granulation tissue with round cell secretions in the meantime. METHODS: Ten temporal bones from the Temporal Bone Foundation, derived from infants aged 5 months to 1 year 11 months, were serially sectioned at 20 microm, saved at 0.2-mm intervals, numbered, and stained with hematoxylin and eosin. Every slide was studied for the presence, nature, and stage of pathologic tissue changes of the middle ear and the mastoid antrum. RESULTS: Pseudocystic granulation tissue was massive in the temporal bone of the 8-month-old child born through thick meconium. Severe changes were present in the temporal bones of two infants aged 5 months, one of which showed traces of AFCC. In the temporal bones of two older children, long-standing changes were minor, one of them still showed traces of AFCC. Fresh acute changes and long-standing histologic changes occurred side by side. CONCLUSIONS: Neonatal otitis media caused by AFCC can give rise to extensive granulation tissue and round cell secretion, which is likely to make the ear susceptible to infectious otitis media. Cumulative development of granulation tissue as a result of infection may lead to blockage of attic aeration and drainage pathways, causing irreversible adhesive otitis media. A data base should be formed of all neonates born through meconium-stained amniotic fluid to allow a comparison with those born through clear fluids. Surgery with the creation of auxiliary aeration pathways becomes advisable in the treatment of ears with massive development of granulation tissue.

Amniotic Fluid↗

Effect of amniotic fluid cellular content on attic aeration pathways: histologic observations of infants aged 2 to 4 months.

HYPOTHESIS: The tissue-fixed amniotic fluid cellular content (AFCC) in the middle ear and mastoid antrum causes foreign body type reactions that may later severely restrict the aeration pathways to the main attic and to Prussak's space. BACKGROUND: It was shown by Aschoff 100 years ago that AFCC remained in the neonate ears and caused sterile otitis media. Recent data show that children born through thick meconium are at risk for large quantities of AFCC entering the middle ear cleft, the ensuing inflammatory reaction being related to the amount of AFCC. Spread of AFCC in the neonate occurred along the aeration pathways with corresponding tissue fixation but further systematic data in young infants are lacking. METHODS: Five temporal bones of three infants aged 2 to 4 months were embedded in celloidin, serially sectioned at 20 microns, and every 10th section stained with Hematoxylin and eosin and mounted on slides. All slides were studied and relevant details of aeration pathways and all compartments photographed. RESULTS: The histologic changes were characterized by the development of masses of pseudocystic granulation tissue, with some remnants of the original AFCC, mainly in the form of fragments of hair. The tympanic isthmus was involved to varying extent, maximally to half of its size. Posterior tympanum and the stapes region had masses of fresh granulation tissue, the maturing of which might cause marked indrawing of the posterior pars tensa and further reduction of the tympanic isthmus. Aeration of Prussak's space was severely involved in two bones, favored by the narrow pathway through the posterior pouch. Features of recent acute or secretory otitis media were associated with the early changes caused by AFCC. CONCLUSIONS: The granulation tissue in this age group is immature and its final fate is decided by the nature of the future ear disease. If the AFCC contamination is slight, the granulation tissue after maturing may appear only in the form of thin cords and sheets, a frequent chance finding in ear surgery. Large amount of AFCC may lead to chronic inflammation, which may predispose the child to recurring middle ear infections during infancy. Further histologic and clinical studies in older infants and young children are needed to find out the final outcome after a massive AFCC contamination of the new-born middle ear.

Amniotic Fluid↗

Attic aeration in temporal bones from children with recurring otitis media: tympanostomy tubes did not cure disease in Prussak's space.

HYPOTHESIS: Blockage of the aeration pathways to the attic may cause circumscribed or widespread alterations that are difficult to diagnose clinically. The narrow route via the posterior pouch to Prussak's space is especially vulnerable to obstruction in recurring otitis media. BACKGROUND: Recent studies of the epitympanic diaphragm and compartments have clarified the anatomy of the attic aeration and drainage pathways and emphasized the role of their patency in the healing process of middle ear infections. In neonatal otitis media, the amniotic fluid cellular content (AFCC) has proved to be a good indicator in outlining the areas where inflammation products concentrate, possibly causing early blockage of ventilation. METHODS: Twenty-eight temporal bones from 14 children were studied; 4 of these children had experienced bilateral recurring otitis media. In the latter group, 1 ear was studied by microdissection and the other by serial sectioning. RESULTS: Prussak's space was involved in all 4 pairs of bones and either contained thick mucus, contained secretion in the process of organization, or was obliterated. The tympanic isthmus was fully obstructed in 1, partially blocked in 2, and open in 5 specimens. CONCLUSIONS: If a thick mature connective tissue mass develops under the epidermal layer of Shrapnell's membrane during an obliteration process of Prussak's space, the condition may stay stable and benign. Severe retraction of Shrapnell's membrane represents a likely forerunner of a retraction pocket cholesteatoma. Systematic otomicroscopy allows early detection, and cure can be achieved by minor surgery. In some children, despite the treatment of recurring otitis media with ventilation tubes, the attic and mastoid can be extensively involved, necessitating atticomastoidectomy and the creation of new pathways for attic aeration.

Autopsy↗

Supratubal recess in neonates and infants.

OBJECTIVE: The fetal development of the supratubal recess and of the tensor fold was described by Hammar in 1902. Recent studies claim that neither structure is regularly present in neonates and controversial views have been presented of the separation of the anterior attic and supratubal recess. The objective of this study is to clarify these issues. METHODS: Twenty temporal bones, 13 neonate and seven infant, were studied either by microdissection of fresh (five bones) or formalin stored (two) specimens, or by serial sectioning after formalin fixation and decalcification (13 bones). The serial sections were cut to 20 microm, every tenth section saved and stained by hematoxylin eosin. RESULTS: In all specimens the separating structure between the anterior attic and supratubal recess was the tensor fold. It was intact in 15 bones while five showed a membrane defect. In vertically oriented folds the recess was deep and in horizontally oriented folds shallow. In 19 bones the tensor fold inserted superiorly to a soft tissue insertion ring of varying thickness and only once directly to a shallow transverse crest. The breadth of the tensor fold near the tensor tendon showed only little variation, whereas its height, and the distance from the tensor tendon to the supratubal tegmen varied in larger limits. CONCLUSIONS: The tensor fold and the supratubal recess are present already in the neonate and thus develop during the fetal period. The shape of the recess is determined by the fold direction and its size grows in conjunction with the other middle ear spaces. The transverse crest has no apparent influence on the position of the tensor fold. The easiest method to study the integrated whole of the anterior attic and supratubal recess is to view them alternatively from the anterior and superior microdissection approaches. Clinically, removal of the tensor fold creates an efficient additional aeration route from the supratubal recess to the anterior attic.

Culture Techniques↗

Concentration of free hCGbeta subunit in serum as a prognostic marker for squamous-cell carcinoma of the oral cavity and oropharynx.

This study was conducted to evaluate the clinical usefulness of serum hCGbeta in the diagnosis and prognosis of patients (n = 59) with cancers of the oral cavity and oropharynx. As a reference marker we used squamous-cell carcinoma antigen (SCCAg). A blood sample was obtained from all patients before primary surgery. Serum hCGbeta was determined by a time-resolved immunofluorometric assay (IFMA) and SCCAg by a solid phase immunoenzymometric assay. Elevated preoperative hCGbeta levels were observed in 8 (14%) and elevated SCCAg in 12 (20%) out of 59 patients. Patients with preoperatively elevated hCGbeta had a shorter recurrence-free survival when compared with those with normal hCGbeta levels (log-rank Chi-squared = 6.83, p =.009), and the risk-ratio for recurrence during follow-up for those was 3.6 (95% CI = 1.29-9.94). In a Cox multivariate model hCGbeta (p = 0.039) and stage (p = 0.044) were independent prognostic factors. SCCAg showed no correlation with recurrence-free survival. We conclude that determination of hCGbeta in serum is a potential marker in the prognostic evaluation of patients with SCC of the oral cavity and oropharynx.

Adult↗

Spread of amniotic fluid cellular content within the neonate middle ear.

Six full-term neonatal temporal bones, with meconium contaminated amniotic fluid aspiration of varying degrees, were serially sectioned at 20 microm and every tenth section was stained by hematoxylin eosin and mounted on slides. All stained sections were studied, the data recorded and relevant details of all compartments photographed. In addition, four normal neonate temporal bones were studied, one by serial sectioning and three by microdissection. The lateral incudomalleal and tensor folds were present in all, membrane defects in the tensor fold were seen in two normal ears. Three ears in the aspiration group had much fetal tissue present rendering Prussak's space small. Four ears with aspiration had remnants of incus intercrural (medial) folds. The amniotic fluid cellular content (AFCC) was sparse or nonexistent in the supratubal recess, Prussak's space and hypotympanum. It concentrated to the areas around the stapes, to sinus tympani and round window niche, to lower lateral attic and posterior pouch, medial attic and in lesser amounts to superior attic, mastoid antrum and air cells. Massive amounts of AFCC in tympanic isthmus and posterior pouch may lead to formation of granulation tissue and blockage of the aeration pathways to attic proper and to Prussak's space. These changes may initiate the development of chronic secretory otitis media in infants.

Amniotic Fluid↗

Histomorphometry and bone biomarkers in cynomolgus females: a study in young, mature, and old monkeys.

Although ovariectomized cynomolgus monkeys are used extensively for studies examining perimenopausal changes in the skeleton, very little is known about the changes that occur naturally during growth and aging in these animals. To evaluate the changes in bone during growth and aging in female cynomolgus monkeys, 29 monkeys ranging from 3 years to >22 years of age were given a bone fluorochrome label and iliac biopsies were collected. Serum and urine were collected at the time of biopsy to determine alkaline phosphatase (ALP), osteocalcin, tartrate-resistant acid phosphatase (TRAP), serum and urinary calcium, estradiol, urinary creatinine, and urinary CrossLaps levels. The biopsies from 8 young (3-4 years of age), 13 mature (11-16 years of age) and 8 old (>22 years of age) were analyzed histomorphometrically. ALP, TRAP, and urinary CrossLaps levels were lower in the mature and old monkeys when compared with the young group. Urinary calcium/urinary creatinine levels increased with age. Bone volume (BV/TV), trabecular number (Tb.N), bone formation rate (BFR), and activation frequency (Ac.f) were greatest in the young monkeys and declined in the older groups. The biomarker and histomorphometric indices in the young animals reflect the growth that was occurring in this group. The older monkeys do not appear to differ significantly between 10 and 22 years of age.

Acid Phosphatase↗

Effect of treatment for 6 months with human parathyroid hormone (1-34) peptide in ovariectomized cynomolgus monkeys (Macaca fascicularis).

A potential negative side effect of intermittent parathyroid hormone (PTH) therapy to treat osteoporosis is the loss of cortical bone concomitant with increased cancellous bone mass. We addressed this issue by studying the effects of PTH on whole-body, axial, and appendicular bone mass in an animal model with haversian cortical bone remodeling. Ovariectomized, young adult female cynomolgus monkeys were assigned to placebo (n = 9) or PTH groups (n = 10). The PTH group received 10 microg/kg synthetic human PTH(1-34) peptide by subcutaneous injection, 3 days/week for 6 months, and the placebo group received vehicle. Multiple endpoints of bone mass, strength, and turnover in the axial and appendicular skeleton were assessed, including dual-energy X-ray absorptiometry (DEXA), quantitative computed tomography (qCT), analysis of serum (calcium, phosphorus, alkaline phosphatase, osteocalcin, and tartrate-resistant acid phosphatase) and urinary (calcium and creatinine) biomarkers, histomorphometry, and biomechanical testing. Compared with placebo-treated animals, PTH-treated monkeys had no change in whole-body bone mass, but a 6.7% increase in spinal areal bone mineral density (aBMD) was observed. Cortical bone mass measured by qCT at appendicular sites was not affected by PTH treatment, but there were significant increases in cancellous bone mass in the proximal tibia, and a similar trend in the distal radius. Small, transient increases in serum and urinary calcium were observed, but there were no treatment-related effects on other biochemical endpoints. Increased bone formation rate (BFR/BV) in the midradius and midfemur was accompanied by a nonsignificant increase in midfemur porosity. Increased vertebral cancellous bone volume (BV/TV) was associated with greater trabecular and interstitial thickness with no effect on wall thickness. Increases in bone strength were observed in both axial (vertebral maximum stress and load at fracture) and appendicular (femoral neck fracture load) skeleton. Together, these results indicate that PTH therapy in the cynomolgus monkey results in a net gain of spinal and appendicular cancellous bone mass with no adverse effect on cortical bone.

Absorptiometry, Photon↗

Chronic inflammatory ear disease and cholesteatoma: creation of auxiliary attic aeration pathways by microdissection.

HYPOTHESIS: The attic compartments, except for Prussak's space, are aerated through the tympanic isthmus. The aim of this study was to develop aeration pathways that would bypass the isthmus in surgery for chronic inflammatory ear disease and cholesteatoma. BACKGROUND: Microdissection of the epitympanum has shown that the anterior attic and the supratubal recess are separated by the tensor fold, the excision of which creates a large new aeration pathway. METHODS: Earlier surgical experience was reexamined as to the access to the tensor fold. Twenty temporal bones were dissected to create clinically useful new surgical routes for tensor fold removal in the presence of an intact ossicular chain. RESULTS: An endaural atticotomy, extended to the supratubal recess, allows excision of the tensor fold; however, the excision must be performed blindly. Cutting the neck of the malleus to allow lateral lifting of the manubrium exposes the tensor tendon and allows rapid excision of the fold. The elasticity of the tendon assists in approximation of the cut edges. In canal wall up surgery, removal of the lateral attic bone until the root of the zygoma exposes the anterior surface of the head of the malleus and the lateral portion of the transverse crest. Drill-out of the crest leads directly to the posterior side of the tensor fold, allowing its excision under direct vision. Thinning of the attic bone lateral to the body and short process of the incus allows simultaneous removal of the lateral incudomalleal fold. CONCLUSIONS: When the ossicular chain is discontinuous, tensor fold resection can be made under direct vision. With an intact chain, cutting of the neck of the malleus used in tympanic glomus tumors causes no hearing changes, allows complete fold excision, and is adaptable to chronic ear surgery. The frontolateral attic route for removal of tensor fold, together with the lateral incudomalleal fold, can be used in the canal wall up surgery to improve attic aeration.

Cholesteatoma, Middle Ear↗

Presentation with multiple cutaneous basal cell carcinomas: association of glutathione S-transferase and cytochrome P450 genotypes with clinical phenotype.

We previously reported associations between numbers of basal cell carcinomas (BCCs) and glutathione S-transferase (GSTM1 and GSTT1) and cytochrome P450 (CYP2D6) genotypes. Thus, although GSTM1 AB is protective, GSTM1 null, GSTT1 null, and CYP2D6 EM are associated with increased numbers of lesions. Here, we examine the hypothesis that these genotypes are associated with high-risk subgroups. The subgroup studied comprised 119 patients with more than one previously unidentified BCC at first or later presentations [multiple presentation phenotype (MPP)]. These patients were part of a group of 773 BCC patients that also included 567 patients with one BCC and 87 patients with only one lesion at each presentation [single presentation phenotype (SPP)] but who developed multiple BCCs. The number of tumors in the MPP was significantly greater than that in the SPP groups. In the MPP but not SPP patients, GSTM1 AB, GSTT1 null, and CYP2D6 EM were significantly associated with BCC numbers, suggesting that previously observed associations reflect the influence of these genes only in the MPP cases. There was no evidence that MPP patients had received more UV exposure. We also determined whether the increased numbers of BCC in the MPP cases reflects an association with the truncal tumor phenotype. The values of the rate ratios indicated that the MPP is a marker for the risk of many BCCs, although the combination of MPP and a truncal tumor is a higher-risk phenotype. The data demonstrate the heterogeneity in BCC patients, which reflects differences in genetic factors that determine skin response to UV.

Adult↗