Effects and treatment of inflammatory bowel disease during pregnancy

QUESTION: I have several patients with inflammatory bowel disease (IBD) who are pregnant or planning pregnancies. What information can I give them regarding the possible effects of IBD on pregnancy and the medications used to treat IBD during pregnancy? ANSWER: Women with IBD appear to be at increased risk of giving birth prematurely, having low-birth-weight infants, and having cesarean sections. Neither 5-aminosalicylic acid nor sulfasalazine has been found to increase the rate of major malformations, fetal mortality, or morbidity. There is conflicting evidence regarding the use of corticosteroids and azathioprine and 6-mercaptopurine. There are limited data on the use of infliximab during pregnancy, although no pattern of defects or complications has been reported to date.     

Epidermodysplasia verruciformis: 14 members of a pedigree with an intriguing squamous cell carcinoma transformation

A 38-year-old farmer was apparently well until 5 years of age. At this age, the patient's mother found mildly itchy, raised eruptions over the scalp during combing of the scalp hair. Since then, the eruptions have progressed insidiously to involve the face and other parts of the body, with a preponderance over the face, upper back, and chest, including the palms. The soles, oral cavity, and genital tract were unaffected. The lesions were persistent in nature and showed no remission or exacerbation. Mild to moderate pruritus/discomfort was experienced following sunlight exposure. A prominent, raised eruption appeared on the right side of the forehead 9 years ago, 25 years after the initial eruptions, which in due course ulcerated. It was progressive in nature and acquired a large size. Two years later, it was diagnosed as squamous cell carcinoma, for which liquid nitrogen cryosurgery was performed. There was a recurrence of the lesion at the site of surgery, which was excised 4 months later. Subsequently, there was a sudden flare up at the same site. It was badly infected with maggot infestation. The relentless course of the disease was evident by the appearance of two similar lesions, one on the right half of the nose and the other on the left preauricular region. A short while ago, fatigue and loss of weight were also recorded. Bladder and bowel functions were normal and there was no loss of appetite, hoarseness of voice, or breathlessness. Four of the patient's six children (three sons and one daughter) were reported to have similar lesions all over the body. In addition, nine other relatives were also affected. Accordingly, a total of 14 (12 males and two females) family members were found to be affected from amongst 41 individuals (26 males and 15 females) spread across several generations (Fig. 1). There was a second-degree consanguinity of marriage, with the patient's grandmother and wife's father being brother and sister. Skin surface examination was marked by multiple, discrete, flat-topped, scaly, brownish-black papules of diverse morphology, from hypopigmented macules to verrucous lesions, with a few coalescing to form plaques. The scales were brown, dry, and adherent (Fig. 2a). The lesions were conspicuous by their presence over the face, neck, and front and back of the chest. The extremities were also affected. Nevertheless, the soles and genitalia were spared. The oral mucosae, hair, and nails were normal. Koebner's phenomenon was explicit, whereas Auspitz's sign was not demonstrable. In addition, a perceptible nodulo-ulcerative lesion (size, 3 in x 2 in) with indurated, raised, averted margins was encountered on the right side of the forehead. The ulcer was tender and had a fetid discharge. Necrotic slough was prominent over its base. Similar lesions were located on the left preauricular region and right half of the nose. Hematoxylin and eosin-stained sections prepared from biopsies taken from representative lesions of epidermodysplasia verruciformis and squamous cell carcinoma revealed their diagnostic features. Epidermodysplasia verruciformis showed features of hyperkeratosis and acanthosis with hardly any papillomatosis. Marginal elongation of the rete ridges was present. Extensive vacuolization was a remarkable feature, and was largely confined to the upper stratum Malpighian and the granular cell layer. Some of the vacuolated cells were fairly large; their nuclei were located in the center and had variable pyknosis. The granular cell layer was uniformly thickened, whereas the stratum corneum had a loosely felted (basket-weave) appearance. The dermis was apparently normal (Fig. 2b,c). The other microsection(s) from squamous cell carcinoma were conspicuous by the presence of hyperkeratosis, acanthosis, and irregular masses of epidermal cells, proliferating downwards and invading the dermis. Varying proportions of differentiated squamous cells formed their bulk. These cells were atypical, characterized by variations in size and shape, hyperplasia and hyperchromasia of the nuclei, absence of prickles, chas, characterization of individual cells, and the presence of both mitotic and atypical mitotic figures (Fig. 3b).     

The Transseptal T‐Cut—What More Can We See?

Abstract   An optimal approach to the mitral valve for repair or replacement must provide adequate exposure even in a small left atrial and redo cases, without need for forceful retraction. This benefit of good exposure must not be at the cost of increased morbidity from increased postoperative bleeding, SA node, or atrioventricular node dysfunction. We describe a simple technique of transseptal T-cut for exposure of the mitral valve, which is without the attendant complications of the other techniques.     

Impact of critical process and formulation parameters affecting in-process stability of lactate dehydrogenase during the secondary drying stage of lyophilization: a mini freeze dryer study

The stresses during the secondary-drying stage of lyophilization were investigated using a controlled humidity mini-freeze-dryer [Luthra S, Obert J-P, Kalonia DS, Pikal MJ. 2007. Investigation of drying stresses on proteins during lyophilization: Differentiation between primary and secondary-drying stresses on lactate dehydrogenase using a humidity controlled mini freeze-dryer. J Pharm Sci 96: 61-70.]. Lactate dehydrogenase (LDH), was formulated in: (1) Tween 80, (2) citrate buffer, and (3) both Tween 80 and citrate buffer. Protein activity recovery was measured as a function of relative humidity (RH), product temperature, and drying duration. Studies were also conducted with different concentrations of sucrose, sorbitol, and poly (vinyl pyrrolidone) (PVP). LDH stability was affected to a small extent by RH and significantly by drying temperature and duration. Complete stabilization of LDH was observed when lyophilized with sucrose and PVP but only a partial stabilization was observed with sorbitol. The mini-freeze-dryer enabled studying the process parameters independently, unlike a conventional study where these effects are generally convoluted. The results suggest that the stability of the protein is a function of the dynamics of the system during lyophilization. The origin of the stabilization effect of sucrose, which could, in principle, be attributed both to direct interaction with the protein or vitrification of the protein was elucidated using lyoprotectants that can either hydrogen bond well with the protein (sorbitol) or form a good glass (PVP). It appears both effects are required for complete stabilization of the protein.     

Investigation of drying stresses on proteins during lyophilization: differentiation between primary and secondary-drying stresses on lactate dehydrogenase using a humidity controlled mini freeze-dryer

This article describes the design, performance testing, and application of a controlled humidity mini-freeze-dryer in studying the physical stability of lactate dehydrogenase during lyophilization. Performance evaluation of the mini-freeze-dryer was conducted with tests, namely water sublimation, radiation heat exchange, lowest achievable temperature, and leak testing. Protein stability studies were conducted by comparing protein activity at various stages of lyophilization with the initial activity. The shelf and condenser temperature were stable at <-40 degrees C, wall temperature was within 2 degrees C of the shelf temperature, and the leak rate was small. The chamber pressure was controlled by the ice on the condenser and the product temperature during sublimation was equal to the shelf temperature. Addition of Tween 80 prevented activity loss in solution and after freeze-thaw. No activity loss was observed after primary-drying even in absence of lyoprotectants and with collapse of cake structure. Five percent (w/w) sucrose concentration was required to achieve full stabilization. In conclusion, performance testing established that the mini-freeze-dryer was suitable for mechanistic freeze-drying studies. Secondary-drying was the critical step for protein stability. The concentration of sucrose required to stabilize the protein completely was several orders of magnitude higher than that required to satisfy the direct interaction requirement of the protein.