Mohammed Ahmed

Silver sulfadiazine based cubosome hydrogels for topical treatment of burns: development and in vitro/in vivo characterization.

The present study is concerned with the development and characterization of a novel nanaoparticulate system; cubosomes, loaded with silver sulfadiazine (SSD), which is the metallic salt of a sulfonamide derivative, and is considered as the drug of choice for topical treatment of infected burns. Cubosome dispersions were formulated by an emulsification technique using different concentrations of a lipid phase monoolein and the nonionic surfactant, Poloxamer 407, with or without polyvinyl alcohol. The prepared cubosomal dispersions were characterized regarding physical morphology, dimensional distribution, particle size, and in vitro drug release. The optimum formulae were incorporated in a chitosan, carbopol 940 or chitosan/carbopol mixture based hydrogels, to form cubosomal hydrogels (cubogels). The cubogels were characterized regarding in vitro release of SSD, rheological properties, pH, and mucoadhesion. For the optimal cubogel formulae, an in vivo histopathological study was conducted on rats to predict the effectiveness of the newly prepared cubogels in comparison with the commercially available cream (Dermazin®). In vivo histopathological study results showed that prepared cubogels were successful in the treatment of deep second degree burn which may result in better patient compliance and excellent healing results with least side effects in comparison with the commercially available product.

Sphenoid Sinus Brown Tumor of Secondary Hyperparathyroidism: Case Report

OBJECTIVE AND IMPORTANCE Brown tumor is a misnomer for a reparative cellular process caused by primary or, less commonly, secondary or tertiary hyperparathyroidism. Atypical involvement of the base of the cranium in the area of the sphenoid sinus and the orbit is exceedingly rare and may produce a neurological deficit as a primary clinical presentation. Those neurosurgeons dealing with cranial base and pituitary lesions should be aware of this disease entity, and it should be listed in the differential diagnosis. CLINICAL PRESENTATION A 21-year-old woman with end-stage renal failure on chronic dialysis was referred to the Department of Neurosciences at King Faisal Specialist Hospital and Research Centre with a 4-month history of progressive impairment of vision, associated with headache and nausea. Computed tomography and magnetic resonance imaging demonstrated an expansive mass lesion in the sphenoid sinus with erosion of the sellar floor and posterior medial wall of the orbit causing compression of the optic nerves. The biochemical laboratory studies showed elevation of parathyroid hormone and confirmed the diagnosis of hyperparathyroidism. INTERVENTION The transnasal-transsphenoidal approach was used for extensive microsurgical removal of the lesion. The postoperative course was uneventful, and the improvement in vision was dramatic. CONCLUSION Brown tumor, although rare, should be listed in the differential diagnosis of expansive mass lesions in the area of the sphenoid sinus and cranial base. The management is multidisciplinary, and therapeutic options should target the underlying cause.

Classical Pituitary Apoplexy Presentation and a Follow-Up of 13 Patients

Thirteen patients who presented with signs and symptoms of pituitary disease gave a history of classical pituitary apoplexy. Six presented with acute symptoms and in 7 the history antedated the admission by a mean of 887 days (range 365-2,190 days). All patients had an enlarged eroded sella. CT scans revealed a bleed in the tumor in 11 (histologically confirmed in all 8 patients operated), evidence of residual tumor in 1 and an empty sella (ES) in 1 patient. Hypopituitarism was present in 9, 4 were endocrinologically normal, 8 had visual problems requiring decompressive surgery and radiotherapy (RT) was given to 7 patients. They were subsequently followed for a median period of 730 days (range 365-3,385 days). During this time an empty sella developed in 5, 2 of whom had no surgery or RT; 4 remained endocrinologically normal, and a second hemorrhage occurred in 2 patients. Histological evidence of previous bleeds was noted in 6 of the 8 patients treated surgically. We conclude that apoplexy (1) may produce complete or partial tumor destruction with or without preservation of endocrine function; (2) recurrent, often silent, bleeding into a pituitary tumor appears to be a common event; (3) RT should be withheld unless recurrent tumor is documented (since at least 2 patients in this study have experienced spontaneous resolution of the tumor); and (4) the presence of an enlarged eroded fossa with an ES is reasonable presumptive evidence of an infarction of a pre-existing pituitary tumor.

Acute and long-term effects of octreotide in patients with ACTH-dependent cushing's syndrome

PURPOSE Octreotide is of proven efficacy in the management of patients with acromegaly, thyrotropin-secreting pituitary adenomas, and certain gastrointestinal tumors, but its effect in Cushings syndrome is less clear. PATIENTS AND METHODS We studied 10 patients who presented with adrenocorticotropic hormone (ACTH)-dependent Cushings syndrome, 3 of whom were previously adrenalectomized. Serum cortisol or ACTH levels were measured before and during the administration of octreotide 50 to 500 micrograms every 8 hours for 24 to 72 hours. RESULTS Treatment was effective in four patients: serum cortisol levels decreased to within or below the normal range in Patients 1, 2, and 3, and ACTH levels were substantially lowered in Patient 4, who had previously been adrenalectomized for a metastatic islet cell tumor. These responses were sustained during long-term treatment for 2 to 72 weeks. All four patients showed no evidence of a pituitary tumor on computed tomographic or magnetic resonance imaging and had proven (Patients 3 and 4) or presumed ectopic disease. Of the six patients who did not respond, four had pituitary tumors and two had presumed ectopic ACTH production. CONCLUSION We conclude that a short trial of octreotide is warranted in patients with ACTH-dependent Cushings syndrome who have no demonstrable pituitary tumor. A response to treatment should alert the physician to the possibility of an ectopic ACTH source and will identify patients whose disease may be controllable using octreotide.

Pituitary Gland Enlargement in Primary Hypothyroidism: A Report of 5 Cases with Follow-Up Data

Five female patients with primary hypothyroidism and radiological evidence of a pituitary enlargement were studied before and after a mean of 30 months (range 12-83 months) treatment with thyroxine (T4). Before treatment, serum thyroid-stimulating hormone (TSH) levels were elevated in every patient (mean 392 mU/l, range 240-475) and prolactin levels in 4 (mean 79 micrograms/l, range 48-143 micrograms/l). CT scanning confirmed the presence of pituitary enlargement in the 4 patients studied, which was suprasellar in 3. The remaining patient had an enlarged fossa on a lateral skull radiograph. During treatment with T4, TSH and prolactin levels were normal in all. Complete disappearance of the enlargement was seen on follow-up scans in all patients and 1 developed an empty sella. The induction of a pituitary enlargement by primary hypothyroidism results from reversible hyperplasia of both the TSH and prolactin-secreting cells in most instances. Occasionally, however, hyperplasia of the thyrotrophs can occur in isolation and an empty sella can occur after successful treatment with T4. Thyroid function tests should be obtained in all hyperprolactinemic patients.

ACTH-producing pituitary cancer: experience at the King Faisal Specialist Hospital & Research Centre.

Pituitary gland is an uncommon site of a primary cancer. Of more than 600 cases of pituitary tumors seen at the KFSH&RC between 1975 to 1998 only 3 patients had primary pituitary cancer. We have previously reported a case of pituitary fibrosarcoma arising as a rare complication of external radiotherapy (ERT) for GH-secreting pituitary adenoma (PA) [1]. We report now 2 cases of ACTH-producing primary pituitary carcinoma (ACTH-PPC); their follow-up data provide information on the natural history of this cancer. Patient #1; a 46 year old lady with Cushings disease (CD) presented with an enlarged right cervical lymph node (LN) 2 years after having undergone a partial hypophysectomy through transsphenoidal surgery (PHYPX/TSS) and ERT for an invasive pituitary tumor. Patient #2; a 26 year old man presented with CD and underwent bilateral adrenalectomy (ADx) and pituitary ERT. Thirty-nine months later he developed Nelsons syndrome and a PHYPX/TSS was performed. Incidentally discovered hepatic metastases in this patient and an excisional biopsy of the LN in patient #1 showed histological features very similar to the pituitary tumor, and they stained strongly positive for ACTH. Perinuclear spherical hyalinized cytoplasmic inclusions were seen in the LN biopsy that corresponded to bundles of type 1 microfilaments (specific for pituitary ACTH-producing cells) seen by electron microscopy. A whole body 18-Fluoro-2-Deoxy-D-Glucose positron emission (FDG-PET) scanning, showed an intense uptake in the neck mass. A trial of octreotide did not change the exceedingly high levels of ACTH in patient #2, further supporting the diagnosis of ACTH-PPC. The clinical course of 102 months prior to his demise showed continued progression of the primary and the metastatic tumor. Patient #1, is alive at 15 months follow-up; hypercortisolemia is controlled using ketoconazole. ACTH-PPC should be entertained in a patient with CD presenting with persistent cervical lymphadenopathy. The clinical course in our patients suggests that the emergence of PC may involve a proliferative continuum from a pre-existing PA to an invasive tumor, culminating in a carcinoma. Adjunctive events such as ERT/ADx may predispose to the evolution of PC in genetically susceptible individuals. Because ERT is an effective treatment for PA its use will continue; it is important to be aware of the possible complication of primary pituitary carcinoma.

Repeated Remissions of Cushing's Disease Due to Recurrent Infarctions of an ACTH-Producing Pituitary Macroadenoma

Infarction of prolactin-secreting or growth hormone-secreting pituitary adenomas is not unusual. However, Infarction of ACTH-secreting adenomas has rarely been reported. Cyclical course of Cushings syndrome alternating with adrenal insufficiency due to recurrent infarction of an ACTH-secreting pituitary adenoma has not been reported. We report here a 20-year-old lady who presented with florid signs of Cushings syndrome but was found to have adrenal insufficiency on biochemical evaluation. Magnetic resonance imaging (MRI) of the pituitary gland showed that she had infarction of an ACTH-secreting macroadenoma. Over the next 6 years, her disease ran a cyclical course characterized by periods of hypercortisolism alternating with adrenal insufficiency due to repeated episodes of infarctions of the ACTH-secreting pituitary macroadenoma with corresponding changes in the pituitary adenoma on serial MRIs. The case alerts clinicians to this possibility when a patient presents with clinical picture of Cushings syndrome but has adrenal insufficiency on biochemical testing. It also suggests that silent or subclinical infarction of pituitary adenomas is not uncommon and is probably under diagnosed.

A study of 875 cases of thyroid cancer observed over a fifteen-year period (1975-1989) at the King Faisal Specialist Hospital and Research Centre.

Thyroid cancer (TC) is a common malignancy encountered at King Faisal Specialist Hospital and Research Centre (KFSH&RC). Of 19,885 different malignant tumors seen during the period fro 1975 to 1989, there were 875 cases (4.4%) of TC. Of 1374 tumors of endocrine glands seen during the same period, 67% were thyroid neoplasms. TC represented 7.5% (618 cases) of all neoplasms in the females, second only to breast cancer. All types of TC were seen, with papillary thyroid carcinoma (PC) being the most common (79%). Anaplastic, medullary, follicular (FC), malignant lymphoma and Hürthle cell cancer accounted for 5.4%, 5.3%, 4.3%, 3.6% and 0.9% respectively. The frequency of PC was very similar (16%) in each of the third, fourth and fifth decades. The relative frequency (RF) of different types of TC was highest for PC with a ration of 18:1 between PC and FC, which could be the highest ever reported. There was a clearly progressive increase in the number of thyroid tumors referred between 1975 and 1989. Although this increase was evident for both sexes, it was more apparent for females. There was also a distinct increase (P<0.01) in the RF of PC from 76% (1975 to 1980) to 85% (1986 to 1989) with a decrease in FC from 9% to 2.5% over the same periods.

Whole-body positron emission tomographic scanning in patients with adrenal cortical carcinoma: comparison with conventional imaging procedures.

Two patients with histologically documented adrenal cortical carcinoma (ACC) underwent whole-body fluorodeoxyglucose (FDG) positron emission tomographic (PET) imaging. Results were compared with those of computed tomography (CT), magnetic resonance imaging (MRI), ultrasound, bone scanning, and octreotide imaging to evaluate the role of PET and to determine any additional advantage PET may provide over conventional imaging in the management of ACC. Both patients were 26-year-old men. One patient was found to have Cushings syndrome, and the other had a clinically silent recurrent ACC. These findings indicate that PET can accurately localize ACC before operation and reliably detect its recurrence after operation. It can serve as an adjuvant imaging method in the detection of metastases and monitor the clinical course of ACC with findings that complement those of conventional imaging. It can yield additional information in defining tumor metabolic activity, necrosis, and in the earlier detection of metastases compared with CT.

PAPILLARY THYROID CANCER IN SAUDI ARABIA: CLINICAL, PATHOLOGIC AND MANAGEMENT CHARACTERISTICS

During a 3-year period, 233 patients with papillary thyroid cancer were seen at King Faisal Specialist Hospital (KFSH) (79% were female; 94% were national subjects). Pathology revealed 88% pure papillary carcinoma and 12% mixed papillary and follicular carcinoma, 7% microfocus, 18% well encapsulated, 24% capsular invasion, and 51% soft tissue invasion. Thirty percent of patients who had initial surgery not done at KFSH compared with 93% of patients who had initial surgery done at KFSH had an I-123 24-hour uptake < 5%. One hundred seventeen patients required completion thyroidectomy at KFSH for significant residual thyroid tissue, 56% of those had residual papillary carcinoma. The amenability of papillary thyroid cancer for cure necessitates the optimization of management at the national level. In Saudi Arabia, papillary thyroid cancer presented in an advanced stage, especially in males as manifested by the large primary tumor size, advance pathologic staging, and distant metastases at the time of presentation. Findings at second surgery, showed significant residual disease.