Breathing life into dinosaurs: tackling challenges of soft-tissue restoration and nasal airflow in extinct species.

The nasal region plays a key role in sensory, thermal, and respiratory physiology, but exploring its evolution is hampered by a lack of preservation of soft-tissue structures in extinct vertebrates. As a test case, we investigated members of the "bony-headed" ornithischian dinosaur clade Pachycephalosauridae (particularly Stegoceras validum) because of their small body size (which mitigated allometric concerns) and their tendency to preserve nasal soft tissues within their hypermineralized skulls. Hypermineralization directly preserved portions of the olfactory turbinates along with an internal nasal ridge that we regard as potentially an osteological correlate for respiratory conchae. Fossil specimens were CT-scanned, and nasal cavities were segmented and restored. Soft-tissue reconstruction of the nasal capsule was functionally tested in a virtual environment using computational fluid dynamics by running air through multiple models differing in nasal soft-tissue conformation: a bony-bounded model (i.e., skull without soft tissue) and then models with soft tissues added, such as a paranasal septum, a scrolled concha, a branched concha, and a model combining the paranasal septum with a concha. Deviations in fluid flow in comparison to a phylogenetically constrained sample of extant diapsids were used as indicators of missing soft tissue. Models that restored aspects of airflow found in extant diapsids, such as appreciable airflow in the olfactory chamber, were judged as more likely. The model with a branched concha produced airflow patterns closest to those of extant diapsids. These results from both paleontological observation and airflow modeling indicate that S. validum and other pachycephalosaurids could have had both olfactory and respiratory conchae. Although respiratory conchae have been linked to endothermy, such conclusions require caution in that our re-evaluation of the reptilian nasal apparatus indicates that respiratory conchae may be more widespread than originally thought, and other functions, such as selective brain temperature regulation, could be important.

Penile intraepithelial neoplasia: clinical spectrum and treatment of 35 cases.

BACKGROUND: Penile intraepithelial neoplasia (PIN) is the term used to describe erythroplasia of Queyrat (EQ), Bowen's disease (BD) and bowenoid papulosis (BP). These conditions are distinct clinical entities and have different epidemiological and aetiological associations and prognostic implications. OBJECTIVES: To describe the presentation and treatment of patients with PIN. METHODS: Thirty-five patients presenting with PIN over a 7-year period are described. RESULTS: Our observations include: (i) patients with BP are younger than those with EQ or BD and sometimes have a history of immunosuppression; (ii) patients with BP usually have a history or clinical evidence of previous genital human papillomavirus infection; (iii) patients with EQ often have a concurrent penile dermatosis (lichen sclerosus or lichen planus); (iv) patients with PIN are usually uncircumcised; and (v) response to treatment of BP depends on the integrity of the immune system. CONCLUSIONS: We recommend vigorous treatment of all patients with PIN, including circumcision. Smoking should be actively discouraged. Patients should have life-long follow-up and partners of patients with BP should be screened for other forms of intraepithelial neoplasia (cervical and anal).

The dysfunctional foreskin.

Although important, the foreskin is not absolutely essential to penile function. Dysfunction is common and a cause of considerable morbidity, and is sometimes associated with mortality from squamous cell carcinoma (SCC). Penile dermatoses herald, complicate or cause preputial dysfunction. Their effective diagnosis and management reduces morbidity and possibly mortality. Medical treatment has its limitations and circumcision is often required.

Barraquer-Simons lipodystrophy, Raynaud's phenomenon and cutaneous vasculitis.

We report a 32-year-old man who presented with a 2-year history of unexplained weight loss and symptoms of Raynaud's phenomenon. Clinical examination and investigations were consistent with a diagnosis of acquired partial lipodystrophy (Barraquer-Simons disease). This patient also exhibited an associated cutaneous vasculitis and peripheral perniotic changes. He had normal renal function and glucose tolerance and no immunological abnormality has been detected in his serum to date. The absence of C3-nephritic factor in the presence of overt lipodystrophy suggests that there may be another factor or immunological mediator responsible for the subcutaneous changes seen in patients with lipodystrophy.

Haematological disease in siblings with Rothmund-Thomson syndrome.

We report two siblings with Rothmund-Thomson syndrome (RTS); the older sister died of acute myeloblastic leukaemia and the younger sister has a slowly progressive leucopenia. Her prognosis is guarded in view of the increased incidence of neoplasms in this condition. More than 200 cases of RTS have now been reported worldwide.1 This is the first report of siblings with haematological disease and RTS.

The perils and pitfalls of penile injections.

We describe a 45-year-old man who presented with an indurated penile nodule following self-injection of acyclovir tablets which he had dissolved in hydrogen peroxide solution. This is a hazardous procedure which may be complicated by permanent deformity and functional disability due to the irritant nature of the tablets' constituents and their propensity to cause foreign body reactions in the skin.

Sarcoidosis in a patient with linear IgA disease.

We report a patient with four conditions in association with linear IgA disease (LAD), only three of which have been reported previously; these latter are ulcerative colitis, autoimmune thyroid disease and carcinoma of the colon, although the carcinoma may have been caused by the ulcerative colitis in this case. Recently, our patient also presented with respiratory symptoms and was found to have sarcoidosis as well, a previously unreported association of this autoimmune bullous disorder. The aetiology of this development may be related to the patient's HLA status or possibly to his treatment with the immunosuppressive agent cyclophosphamide; it is also possible that it is coincidental.

Renal function after 10 years' treatment with cyclosporin for psoriasis.

Renal function was assessed by measuring serum creatinine and glomerular filtration rate (GFR) in two groups of patients with chronic plaque psoriasis who had been treated with cyclosporin A (CyA), average dose 2.8 mg/kg per day (range 1-5 mg/kg per day). Group I was our original cohort of nine patients, seven of whom had received CyA for an average period of 10 years (range 9.5-11 years). These seven patients showed a persistent increase in serum creatinine > 30% from baseline measurement and four of the seven had persistent increases > 50%. The GFR, which was first measured after 2.5 years of treatment, showed at 10 years a decrease of > 30% in two patients and of > 50% in one patient. Three of the seven showed stable renal function while two had repeat renal biopsy because of deteriorating renal function and histology showed further evidence of CyA nephrotoxicity compared with that after 5 years' treatment. Two of the nine patients in group I had discontinued CyA 5 years previously after 5 years of treatment because of CyA nephrotoxicity on renal biopsy and impaired renal function. This impairment of renal function showed improvement during the 5 years of follow-up, implying reversibility of CyA nephrotoxicity. The second group of 20 patients had received CyA for an average duration of 6 years (range 5-8 years). Nine of the 20 patients showed persistent increases in serum creatinine of > 30% from baseline and five showed persistent increases of > 50%. The GFR showed a persistent decrease of > 30% in seven patients and of > 50% in two patients. This study has shown that nephrotoxicity is associated with long-term treatment with CyA. However, there is patient variation as to when nephrotoxicity commences and its speed of progression. On discontinuing CyA the impairment of renal function improves with time. Providing renal function is monitored with GFR and renal biopsy in addition to serum creatinine then long-term (5-10 years) CyA treatment can be justified in severe psoriasis not responsive to other treatments.